Key Takeaways

• In an anonymous online survey of 343 participants, the majority (83%) of respondents no longer met the criteria for alcohol use disorder (AUD) after taking part in an experiment involving the consumption of a moderate or high dose of LSD (38%) or psilocybin (36%) in a non-clinical setting.
• Clinical trials have demonstrated that psilocybin has the potential to break down an individual's habitual thought pattern. Some refer to this phenomenon as "resetting the brain."
• The most common side effects of psilocybin consumption are nausea, increased blood pressure, confusion, fear, and paranoia.

Introduction

Psilocybin For Alcohol Addiction

• Alcohol causes approximately three million deaths annually. Because there are only four approved medications used for the treatment of AUD, and because these treatments demonstrate limited effectiveness, there is an urgent need for better alternatives.
• Psilocybin has emerged as a strong candidate due to some limited evidence that it can contribute to behavioral change in alcohol addiction, as well as other dependencies. However, despite growing interest, preclinical studies on the substance are still relatively scarce.

• The compound's mechanism of action is currently being investigated and is not yet fully understood. Clinical trials have demonstrated that it has the potential to break down an individual's habitual thought pattern. Some refer to this phenomenon as "resetting the brain."
• Brain-imaging technology has demonstrated that psychedelic substances such as psilocybin have the ability to "quieten" the brain's established "default settings" that regulate aspects such as memory, self-reflection, and self-talk. If the compound does influence the brain to break its routine, this could explain how it may be beneficial for addictions — by altering an individual's ingrained thought patterns.
• Furthermore, there may be less measurable benefits, such as feeling more connected to others and being more appreciative of the world around, as well as deeper self-reflection. Those effects can linger for months after the consumption, which may help battle addiction and address its underlying causes. It is also worth noting that according to research, the more mystical the perceived experience, the better the outcomes.
• The above is acknowledged by medical experts as well. For instance, Dr. Michael Bogenschutz, a psychiatrist at New York University’s Grossman School of Medicine, says about psilocybin-assisted therapy for alcohol addiction, "What’s fascinating to me about this whole process is how many different kinds of experiences people can have, which ultimately help them make these profound changes in their behavior."

Research at the University of Heidelberg

• The study was conducted by researchers from the University of Heidelberg. The research team treated rat models addicted to alcohol with psilocybin — the results were promising.
• The research team was successful in treating the dependency through a regimen of psilocybin. It was reported that the compound was effective compared to a control treatment. In addition to reducing cravings, the therapy reduced alcohol-seeking behavior as well as the risk of relapse.
• The researchers attribute the beneficial effects of psilocybin to its ability to restore the expression of a glutamate receptor called mGluR2. According to them, "reduced expression of this receptor causes alcohol cravings and impairments in "executive functions" (e.g. self-control and decision-making)."

Psilocybin-Assisted Treatment for Alcohol Dependence: A Proof-of-Concept Study

• The proof-of-concept study involved a group of ten volunteers officially diagnosed with alcohol dependence. Participants were orally administered psilocybin and provided with Motivational Enhancement Therapy (MET) sessions "devoted to preparation for and debriefing from the psilocybin sessions."
• While alcohol abstinence did not increase significantly within the first four weeks of treatment (prior to administration of psilocybin), abstinence had increased significantly following the administration of psilocybin, and gains were "largely maintained at the follow-up to 36 weeks".
• The intensity of the effects in the first session during week four strongly predicted change in drinking patterns during the weeks ahead (weeks four to five), predicting reductions in cravings and increases in abstinence.

 

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• No significant adverse effects related to the treatment were reported, though this may be due to the small sample size of participants (10).
• The preliminary findings serve as a foundation and rationale for controlled trials with larger sample sizes to investigate the full extent of the efficacy of psilocybin treatment and its mechanism of action.

Online Survey by John Hopkins University of Medicine

• In an anonymous online survey of 343 participants, conducted by the John Hopkins University of Medicine, the majority (83%) of respondents no longer met the criteria for AUD after taking part in an experiment involving the consumption of a moderate or high dose of LSD (38%) or psilocybin (36%) in a non-clinical setting.
• Although the results of the survey cannot demonstrate causality, the results suggest that the use of naturalistic psychedelics (e.g., psilocybin) may lead to a reduction or an overall cessation of alcohol misuse, supporting "further investigation of psychedelic-assisted treatment for AUD."

Side Effects

• The most common side effects of psilocybin consumption are nausea, increased blood pressure, confusion, fear, and paranoia.
• Several study participants reported difficult experiences whilst on the compound. To minimize risk, experts have warned against using the substance outside of research studies without proper medical supervision. However, even in a supervised environment (e.g. a research laboratory), reports of negative side effects such as loss of coordination and anxiety, or even a psychotic break are not uncommon.
• In a John Hopkins survey of almost 2,000 respondents who said that they had a negative experience after the consumption of psilocybin, 10.7% of them said that they believed that their worst "bad trip" had put others or themselves in harm's way. 2.6% of respondents said that they had acted violently or aggressively during their worst "bad trip," while 2.7% said they ended up seeking medical help.
•  Five participants with self-reported preexisting depression, anxiety, or suicidal thoughts had attempted suicide while on the drug during the worst "bad trip." According to researchers, the results are indicative of the importance of having a supportive environment while under the influence of psilocybin in order to minimize risk.
• For additional context, the National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Services Administration reported that approximately 22.9 million Americans (8.7% of Americans) had used psilocybin previously.

Research Strategy

Key Takeaways

• A February 2022 report published in the Journal of Psychopharmacology concluded "that many – albeit not all – of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context." The authors state that much of the concern about psychedelics and suicidal thoughts is based on the stigma of the drugs, rather than on factual evidence.
• In the 1950s and 1960s, there was significant research into the use of psychedelics, and much of the research was promising. However, recreational use in the 60s led to the substances becoming illegal, which dampered research.
• Specifically related to decriminalizing drugs, including psychedelics, California State Senator Scott Wiener stated, "We are working very hard to end the war on drugs — which is an artificial construct that erases a lot of cultures, and also is incredibly racist, and has fueled mass incarceration of Black and brown communities. We need to stop trying to arrest our way out of drug issues, because it does not work.”
• Psychedelics' classification as Schedule I controlled substances means that there are more hoops companies must jump through in order to get approval to conduct studies using the substances. However, in 2018, the Drug Enforcement Administration (DEA) took steps to streamline the approval process. According to Robert W. Patterson, the acting DEA Administrator at the time of the announcement, "We are committed to finding new and innovative ways to meet the needs of the research community. Research is the bedrock of science, and we will—as we have for many years—continue to support and promote legitimate research with Schedule I controlled substances.”
• Kurt Rasmussen, chief scientific officer at Delix Therapeutics, Inc., stated that big pharma was "sitting on the sidelines for now, letting us sort out the risk and all the barriers before it gets involved."

Introduction

Increased Risk of Suicidal Thoughts

• In late 2021, a study of 233 participants taking psilocybin found that a 25mg dose of the drug had a positive impact on depression, as compared to lower doses. However, three participants in the 25mg group displayed suicidal behavior, while two members of the group reported suicidal ideation. While it was not possible to determine that the drug caused these issues, it brought up concerns that need to be further examined.
• There have been media stories linking psychedelic use to suicide, which were then propagated regardless of whether there was data to support the idea. One prominent story from the 60s was the suicide of Diane Linkletter. Her father claimed that she was under the influence of LSD at the time, although this was not confirmed. Regardless, Art Linkletter became a crusader against the dangers of illegal drugs and spread stories that were widely seen by the public.
• Other scientific papers and articles were published through the years that attempted to show a link between psychedelics and suicidal thoughts/actions. One from 2013 discusses a causal relationship between the two; a 2009 publication from the National Institute on Drug Abuse linked PCP use to suicide; and a 2010 article in Scientific American stated, "Hallucinogens can sometimes induce anxiety, paranoia or panic, which in unsupervised settings can escalate to accidental injuries or suicide."
• A meta-review published in March 2021 found that studies showed a mixture of positive, negative, and no association between psychedelics and suicidal thoughts.
• More recent studies that looked at any relationship between psychedelics and suicide have often found that there is no connection, or that the drugs may actually reduce suicidal thoughts. In this study from 2020, "significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use," were found. A meta-analysis from 2022 found that the use of psychedelics actually reduced suicidality.
• A February 2022 report published in the Journal of Psychopharmacology concluded "that many – albeit not all – of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context." The authors state that much of the concern about psychedelics and suicidal thoughts is based on the stigma of the drugs, rather than on factual evidence.
• Multiple recent studies have found that psilocybin may actually reduce suicidality. Examples can be seen here, here, and here.

Lingering Stigmatization

• In the 1950s and 1960s, there was significant research into the use of psychedelics, and much of the research was promising. However, recreational use in the 60s led to the substances becoming illegal, which dampered research. The following chart shows the number of scientific papers published by year, specifically on psilocybin, from 1958 through 2016.

 

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• The main reason behind making the substances illegal was the association with the "hippie" counterculture in the US. Partially due to widespread media coverage of the substances in the US, as well as popular musicians such as Bob Dylan and the Beatles showing interest, the "hippie" culture embraced psychedelics.
• The "hippie" culture was seen as a threat in the US because it demonized much of the traditional American values and norms. For example, they were seen as being against materialism, traditional families, and the Vietnam war. This ultimately led to the war on drugs, and a media push to label psychedelics as dangerous.
• Multiple recent studies and reports discuss how there continues to be a stigma against psychedelics. Examples can be seen here and here.
• One survey from mid-2021 found that 65% of survey respondents did not believe psychedelics have any medical uses.

 

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• However, it appears that this stigma may be lessening, as a 2022 research report found that from 2015 to 2019, hallucinogen use increased from 4.69 million to 6.01 million in the US. Additionally, 65% of Americans who suffer from mental health issues think psychedelics should be available as a treatment option. Of the respondents, 62% said they would try psilocybin.

Legal Issues

• Experts have long seen the legal framework surrounding drug use as a political issue. An article published by the Dulwich Centre (an Australian entity that was established in 1983 and focuses on "narrative approaches to therapy and community work") discusses how the financial incentive associated with drugs means that governments use their power to control the use of these substances. The study titled 'Political Ideologies and Drug Policy,' discusses how coffee was illegal from 1919 to 1933 because it "stigmatized a drug [and] the emerging working class Catholics and their way of life;" cannabis was stigmatized due to "society's rejection of the youth culture and its protest against the established order;" and debates regarding the legalization of harder drugs "mirrors the ideological conflict between the liberal emphasis on individual rights and the paternalistic attitudes of socialists who believe in the government's obligation to protect the adult population."
• In 2013, Attorney General Eric Holder announced that "the Justice Department will no longer pursue mandatory minimum sentences for certain low-level, nonviolent drug offenders." However, Attorney General Jeff Sessions reversed this policy in 2017. This appears to be a reflection of the impact of politics since Holder worked under a Democrat Administration, while Sessions was in a Republican administration.

• States seemed to have agreed with Holder's policy overall, as they had already been leading the way in easing drug laws.

 

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• Data from 2014 found that the majority of Americans favored providing treatment for illegal drugs rather than punishment.

 

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• Specifically related to decriminalizing drugs, including psychedelics, California State Senator Scott Wiener stated, "We are working very hard to end the war on drugs — which is an artificial construct that erases a lot of cultures, and also is incredibly racist, and has fueled mass incarceration of Black and brown communities. We need to stop trying to arrest our way out of drug issues, because it does not work.”
• Graham Boyd, co-founder and executive director of the Psychedelic Science Funders Collaborative, stated, "There really isn’t a legal impediment to ending the arrest of people who use psychedelics; it’s a political one. Each state has the power to change its law, and municipalities have the power to instruct their police to deprioritize arresting people who use psychedelics. Politically there are some very serious obstacles, but legally there is not.”
• Since psychedelics work in conjunction with therapy in order to achieve the desired outcome, labeling substances is a challenge as it is different from what the FDA has done in the past. According to Amy Emerson, CEO of MAPS Public Benefit Corporation, "The FDA was unsure what to do with the therapy part of it. Do they look at the therapy training program? What is the label going to say? How much do you put in the REMS [Risk Evaluation and Mitigation Strategy] and how much do you put in the label?"
• Psychedelics' classification as Schedule I controlled substances means that there are more hoops companies must jump through in order to get approval to conduct studies using the substances. However, in 2018, the Drug Enforcement Administration (DEA) took steps to streamline the approval process. According to Robert W. Patterson, the acting DEA Administrator at the time of the announcement, "We are committed to finding new and innovative ways to meet the needs of the research community. Research is the bedrock of science, and we will—as we have for many years—continue to support and promote legitimate research with Schedule I controlled substances.”

Additional Relevant Findings

• Although we couldn't explore additional controversies surrounding psychedelics within the scope of this request, it was found that one controversy in the medical arena is potential risks to pharmaceutical companies. Kurt Rasmussen, chief scientific officer at Delix Therapeutics, Inc., stated that big pharma was "sitting on the sidelines for now, letting us sort out the risk and all the barriers before it gets involved."
• Rasmussen also said, "bringing some of [pharma's] resources to the problem would be wonderful, [but] that's not going to happen until we sought out a lot of detail, because this could be a risky place for big pharma."
• Frank Wiegand, chief medical officer at Beckley Psytech stated, "The pharmaceutical industry is very opportunistic. I think they will jump on board or will be interested in at least staying very close to what's happening."

Research Strategy

Key Takeaways

• According to the American Journal of Medicine, FDA approval of psychedelics would be conditioned on strict safety requirements to ensure their safe use. Drug-assisted therapy by a professional may be one way to control the use of psychedelics. That is why sponsors of psychedelics research, like the Multidisciplinary Association for Psychedelic Studies (MAPS), are only seeking approval for drug-assisted therapy where specially trained professionals administer the drug in clinical settings and conduct guided therapy sessions.
•  Stephen Ross, MD, associate director of NYU Langone Center for Psychedelic Medicine, stated that "within maybe three to five years, psilocybin is going to be available as a prescription medication.
•  Brad Burge, director of strategic communications for the Multidisciplinary Association for Psychedelic Studies (MAPS), says there’s more funding for studies on the benefits of MDMA and that “we’re going to have prescription-drug approval for psychedelics like MDMA before we have FDA approval for cannabis."
• On February 1, 2022, activists keen to reform drug laws in Michigan proposed a ballot initiative. The initiative identified ibogaine, psilocybin, peyote, psilocin, and dimethyltryptamine as “Natural Plants and Mushrooms,” making them legal for anyone over 18 years to possess, cultivate, use, or gift. The initiative proposes the implementation of a system of regulated sale and treatment, including a hospital that has received a “Certificate of Need” from the Michigan Department of Health and Human Services taking charge.

Introduction

Proposed State Laws To Effectively Control Psychedelics

• The use of psychedelics may be controlled at the state level. Several states have recently taken steps to update their legislation around such substances, which will impact how their use is regulated.
• A report commissioned by the State of Connecticut recommends only approving psilocybin treatments in a licensed clinical setting after it gets FDA approval. It also notes that thorough screening of candidates will be required.
• In New Jersey, the Legislature will develop a long-term statewide strategic plan and a comprehensive regulatory scheme that ensures psilocybin services offer a safe, accessible, and affordable treatment option for those ages 21 and above that need this kind of treatment. The law will ensure drugs will be accessed in safe, controlled environments. Laws will also be developed touching on licensing and regulating psilocybin product manufacturers and service providers and preventing the unlawful diversion of psilocybin in the state.
• In Iowa, the HF636 bill was introduced in February 2021. It proposes creating a Psilocybin Services Act that will guide the regulated administration of psilocybin products to people aged 21 years and older in the state. The bill would stop prioritizing criminal prosecution of noncommercial activities related to psychedelics such as ibogaine, psilocin, mescaline, psilocybin, and peyote. The bill was referred to the House Public Safety Committee.
• In Massachusetts, statewide law has been introduced to study the legalization of entheogenic plants and fungi. In addition, personal use and possession of entheogenic plants have been made the lowest law enforcement priority in Cambridge, Easthampton, Somerville, and Northampton.
• On February 1, 2022, activists keen to reform drug laws in Michigan proposed a ballot initiative. The initiative identified ibogaine, psilocybin, peyote, psilocin, and dimethyltryptamine as “Natural Plants and Mushrooms,” making them legal for anyone over 18 years to possess, cultivate, use, or gift. The initiative proposes the implementation of a system of regulated sale and treatment, including a hospital that has received a “Certificate of Need” from the Michigan Department of Health and Human Services taking charge.
• According to MAPS acting director, Ismail Lourido Ali, “Lawmakers around the country are realizing that it is time for a change in psychedelic policy. Seeing lawmakers in states pass a bill to research the risks and benefits of certain psychedelic substances is a sign that the public perception about psychedelics is being transformed from one of stigma to one of curiosity.”

 

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How Prescribing Psychedelics May Be Regulated on the Federal Level

• According to the American Journal of Medicine, FDA approval of psychedelics would be conditioned on strict safety requirements to ensure their safe use. Drug-assisted therapy by a professional may be one way to control the use of psychedelics.
• That is why sponsors of psychedelics research, like the Multidisciplinary Association for Psychedelic Studies (MAPS), are only seeking approval for drug-assisted therapy where specially trained professionals administer the drug in clinical settings and conduct guided therapy sessions.
• To control the use of psychedelic drugs, some companies are working on modifying them to allow for patent claims. For example, several companies are working "to develop analogs that have a quicker onset and shorter duration." Creating drugs that produce results in less time could help make treatments with psychedelics more widely accessible. However, the modified drugs will need several clinical trials, FDA approval, and re-scheduling before clinicians are allowed to administer them.
• After psychedelic drugs are legalized, they will still face control measures imposed by the Drug Enforcement Administration (DEA). DEA will use the Controlled Substances Act to determine which category psychedelic drugs should be placed into based on assessments of their risks.
• In addition, it will be difficult to change laws to allow physicians to legally prescribe psychedelic substances. Prescribing psychedelics for conditions other than what the drug was approved for by FDA (off-label prescriptions) could be especially problematic.
• While research suggests psychedelic drugs may be beneficial for healthy individuals, medical practitioners may face criminal penalties for prescribing them with no “legitimate medical reason.” Furthermore, DEA does not define what the reason could be.

Expert Perspectives on How Prescribing Psychedelics May be Regulated on the Federal Level

• Some experts think that once legalizes, psychedelics will only be available on prescription. For example, while speaking at the American Psychiatric Association’s annual meeting on psilocybin for treating depression and anxiety, Stephen Ross, MD, associate director of NYU Langone Center for Psychedelic Medicine, stated that "within maybe three to five years, psilocybin is going to be available as a prescription medication, it will be limited by the Risk Evaluation and Mitigation Strategies program at FDA and there will probably be a big regulatory framework."
•  Brad Burge, director of strategic communications for the Multidisciplinary Association for Psychedelic Studies (MAPS), says there’s more funding for studies on the benefits of MDMA and that “we’re going to have prescription-drug approval for psychedelics like MDMA before we have FDA approval for cannabis” as MDMA only has to clear one more major obstacle before it’s officially recognized as medicine. His opinion confirms what was stated above, that patients will not be able to purchase psychedelics from a pharmacy, as the prescription will be for MDMA-assisted therapy.
• Nick Kadysh, CEO of PharmAla, thinks MDMA therapy could be legalized in 2023, and MDMA analogs could be legalized as standalone pharmaceuticals. He states that "right now the protocols are being explored for generic MDMA. However, the drug will most likely be administered at a psychotherapist's office."

Research Strategy

Key Takeaways

• The Oregon Psilocybin Services Section implemented Ballot Measure 109, which mandates the Oregon Health Authority (OHA) to provide psilocybin services and license and regulate the manufacturing, transportation, sales, and purchase activities. It will start accepting applications to manufacture, sell, purchase, and provide psilocybin therapy services on January 2, 2023.
• Based on a 2005 decision in New Mexico, the State Court of Appeal holds that "growing fresh psilocybin mushrooms does not constitute illegal drug "manufacturing."
• In 2019, Colorado became the first state in the U.S. to deprioritize law enforcement actions for possessing small quantities of psilocybin mushrooms (four grams or less) after the enactment of Initiative 301, which prevents from using the state's resources for penalties related to possessing psilocybin mushrooms by adults 21 years and above.

Introduction

 

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Legalization and Regulation Statute — Oregon

• In November 2020, Oregon became the first U.S. state to legalize psilocybin use and decriminalize its possession.
• The Oregon Psilocybin Services Section implemented Ballot Measure 109, which mandates the Oregon Health Authority (OHA) to provide psilocybin services and license and regulate the manufacturing, transportation, sales, and purchase activities.
• The state allowed a two-year development period (January 2021 through December 2022), during which the OHA will collaborate with the Oregon Psilocybin Advisory Board to implement Measure 109 and the use of psilocybin products and services.
• Oregon will start accepting applications to manufacture, sell, purchase, and provide psilocybin therapy services on January 2, 2023.
• On February 1, 2021, Oregon's Measure 110, the Drug Addiction Treatment and Recovery Act, went into effect. It reclassified possession of small amounts of psilocybin as a civil offense that attracts a $100 fine and possession of large quantities from a felony to misdemeanor possession. However, commercial drug activities will attract criminal penalties.

Reduced Penalty Statute — Colorado and New Jersey

• In 2019, Colorado became the first state in the U.S. to deprioritize law enforcement actions for possessing small quantities of psilocybin mushrooms (four grams or less) after the enactment of Initiative 301, which prevents from using the state's resources for penalties related to possessing psilocybin mushrooms by adults 21 years and above.
• In December 2021, activists introduced Initiatives 49 and 50, which sought to create psychedelic treatment facilities. These initiatives were later updated by Initiatives 58 and 59 in January 2022 to create a new approach to natural medicines and establish the Natural Medicine Advisory Board to advise the state on establishing natural medicines 'healing centers.'
• In January 2022, activists filed Initiative 61 to legalize the cultivation, possession, and use of "psilocybin, psilocin, ibogaine, mescaline, and dimethyltryptamine by people aged 21 and older."
• In March 2022, the state introduced the HB 22-1344 bill to legalize and decriminalize possessing, prescribing, dispensing, transporting and using drugs containing 3,4-methylenedioxymethamphetamine (MDMA) and those exempted from the newly enacted provisions.
• In February 2021, the State of New Jersey passed Senate Bill S3256, the Psilocybin Behavioral Health Access, and Services Act, amending the existing law to reduce the penalty for possessing or using psilocybin.

• The new provision stated, "Possession of one ounce or less of psilocybin is a disorderly person's offense." Such an offense is "punishable by up to six months imprisonment, a fine of up to $1,000, or both."
• Before the new amendment, possessing any amount of psilocybin was a third-degree crime punishable by a fine of up to $35,000 or 3-5 years imprisonment.
•  Washington DC also passed the reduced penalty statute.

Limited Judicial Exceptions — New Mexico and New Hampshire

• Based on a 2005 decision in New Mexico, the State Court of Appeal holds that "growing fresh psilocybin mushrooms does not constitute illegal drug "manufacturing."
• The state still claims that the intent to manufacture and sell mushrooms is a felony. According to the state, manufacturing includes additional activities like packaging and labeling containers.

• In The State of New Hampshire v. Mack, the New Hampshire Supreme Court on December 22, 2020, determined that the lower court failed to address that a man found guilty of possession of psychedelic mushrooms used them in a religious context, vacating his conviction. The man was a part of the Oratory of Mystical Sacraments branch of the Oklevueha Native American Church.
• The court proposed that a "balancing test" should be performed between respecting "religious freedom" and "government interest" (i.e., anti-drug laws). The ruling also stated that "New Hampshire’s state constitution is stronger than the federal constitution in upholding religious liberty, because it expressly protects not only religious belief but also religious practices."

Additional Findings

• States currently pursuing new legislation regarding psychedelics include Kansas, Missouri, Oklahoma, Michigan, New York, Vermont, Pennsylvania, Massachusetts, Maryland, Rhode Island, Georgia, Florida, and Iowa.

Research Strategy

Key Takeaways

• According to the 2021 article by Robert Lamb, the stoned ape hypothesis has become a focus of psychedelic culture. Notable advocates like Dennis direct focus on scientific advancements in areas like neuroplasticity and epigenetic inheritance that may continuously explain the means involved in “psychedelics-assisted cognitive advancement.”
• Dennis McKenna, Terence's brother, states that after nearly 30 years, the stoned ape hypothesis has garnered more support than ever because of the knowledge that has been gained since then. He, however, emphasizes that the hypothesis is not intended to be provided as the single factor in human evolution.
• A research paper published in Volume 16 issue 1 of the California Institute of Integral Studies' Journal of Conscious Evolution focuses on exploring McKenna's stoned ape hypothesis and addresses it in relation to the unfolding of human language while including a short introduction to linguistic relativity to demonstrate how many great scholars and thinkers argued that language has molded our worldview.
• A research article by José Manuel Rodríguez and Michael James Winkelman, published in the Frontiers in Psychology journal on September 29, 2021, looks to advance the knowledge of psychedelics and their contribution to human evolution.

Introduction

 

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1. The Stoned Ape Hypothesis: Did Magic Mushrooms Influence Human Evolution?

• In his article published in 2021, Robert Lamb tries to assess the credibility of the stoned ape hypothesis by collecting the statements of different experts and individuals in the space. Among others, he presents Dennis McKenna's (Terence McKenna's brother) opinions on the theory from email communications. Dennis is an “ethnopharmacologist and research pharmacognosist, as well as the founder of the McKenna Academy of Natural Philosophy.”
• According to the article, Dr. Thomas Falk, an Education and Philosophy professor at the University of Dayton, states that the hypothesis explains the creative explosion that happened 40,000 years ago among Homo Sapiens before their migration from Africa to Europe.
• Falk also notes that even though there is no deficiency of theory and evidence surrounding the process of human evolution, the transition to self-consciousness is still a mystery. Therefore, the stoned ape hypothesis offers a key explanation that seems to relate to the existing scientific theory and evidence.

• The article also mentions mycologist Paul Stamets, who argues that mushrooms may have allowed ancestors to create connections between meanings, symbols, and sound, which is the foundation of the creative explosion: “human language, symbol manipulation, and communication.”

• The article reveals that the stoned ape hypothesis has become a focus of psychedelics culture. Notable advocates like Dennis direct focus on scientific advancements in areas like neuroplasticity and epigenetic inheritance that may continuously explain the means involved in “psychedelics-assisted cognitive advancement.”

• Dennis states that after nearly 30 years, the stoned ape hypothesis has garnered more support than ever because of the knowledge that has been gained since then. He, however, emphasizes that the hypothesis is not intended to be provided as the single factor in human evolution. He believes that if mushrooms were present and helped propel humans into history, as we transition into post-historical existence, they are here to guide us in this process.

• The article concludes that the stoned ape hypothesis has little likelihood of advancing to the scientific theory level in the near future, but the form of modern psychedelic reconnection that Terrence McKenna and others advocated could come to pass, especially as more studies assess possible therapeutic uses.

2. An Exploration of Linguistic Relativity Theory for Consideration of Terence McKenna’s “Stoned Ape Theory” on the Origins of Consciousness and Language: Implications for Language Pedagogy

• The research paper was published in Volume 16 issue 1 of the California Institute of Integral Studies' Journal of Conscious Evolution on November 7, 2020. The author is Nicole Lopez.

• The article focuses on exploring McKenna's stoned ape hypothesis and addresses it in relation to the unfolding of human language and consciousness while including a short introduction to linguistic relativity to demonstrate how many great scholars and thinkers argued that language has molded our worldview.
• Lopez states that the linguistics relativity theory is of great significance when examining the origin of language according to McKenna since it establishes the foundation of human beings' ancestral lineage.
• A reflection of the impact of the hypothesis on research in language instruction is given in relation to Lopez's position of research inquiry. She states that the stoned ape theory is most significant to her understanding of the link between language, its origin, and the sprouting of higher forms of human consciousness.
• According to the article, McKenna's case for the impact that plants and mushrooms have had on determining human consciousness, especially language, is strong. However, the degree of influence remains questionable. Lopez also states that if McKenna's hypothesis is to be considered in relation to shamanism and entheogenic use as the root of manifestations of evolved consciousness evidenced via language, then utterance and symbolism hold unimaginable significance.

• Lopez's final position is that the stoned ape hypothesis should be regarded as worthy of deep consideration in the field of Consciousness Studies since it seems to provide valuable views in the current consciousness discourse.

3. Psychedelics, Sociality, and Human Evolution

• A research article by José Manuel Rodríguez and Michael James Winkelman, published in the Frontiers in Psychology Journal on September 29, 2021, looks to advance the knowledge of psychedelics and their contribution to human evolution.

• The article admits that the stoned ape theory has received little attention and needs to be examined further, which is done in the paper.

• The paper, thus, aims to contribute to additional developments so that the hypothesis can be empirically tested.
• This is done by developing an evolutionary model of the “adaptive utilization of psychedelics that properly integrates current anthropological and neuropsychopharmacological knowledge on these substances with the human evolutionary behavioral sciences.”
• The article recognizes that a simple version of McKenna's stone ape hypothesis as the account of human evolution, which implies that only the use of psilocybin inevitably led to the existence of the “unique cognitive, communicative, and cooperative patterns characteristic of modern human populations,” is false. The argument is that hominin transition into the socio-cognitive state cannot be explained by a single causal factor or a crucial adaptive feature such as the use of psychedelics.

• However, this transition was caused by positive feedback loops connecting different aspects of life. From a coevolutionary and multifactorial viewpoint, the article proposes that psychedelics merely enabled human evolution and adaptation.

 

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• Finally, the paper provides a topic that needs further attention. This is psychedelics' role in human brain evolution, which could explain how they may have helped with the release of energetic constraints which were crucial for humans to conquer the metabolic barriers to brain expansion. Entheogens could have established the positive feedback loops with major features of the evolving life (such as tool-use, bipedality, and cooking), fueling the coevolving dynamic that then structured human evolution.

• The suggestion is that psychedelics supported the development of socially constructed environments, acting as an enabler of the establishment of “the human socio-cognitive niche.” Ritual alterations of social bonding, healing, and decision-making activities were expanded, and this increased the propagation of major biological components of sociality, cognition, and communication skills spread in our lineage.

Research Strategy

Key Takeaways

• Based on the discovery of ancient specimens of the cactus Lophophora williamsii in Texas, researchers speculate that peyote was already used by indigenous people in North America 5,700 years ago. 
• Andean cultures have consumed the cactus called "huachuma" for millennia. As a result of the colonization, it acquired a new name, San Pedro. The tribes likened it to Saint Peter, the gatekeeper of heaven, believing that huachuma is "the gate to the spiritual realm" and a way "to achieve heaven on Earth."
• In the Aztec culture, the word for mushrooms was "teonanatacl," which can be translated as "god's flesh." They were used in healing and religious practices, celebrations, and festivals from 3,500 BCE.

Introduction

The First Known Uses of Psychedelic Plants and Mushrooms

• While researchers can trace back the use of many psychedelic plants and mushrooms thousands of years back and provide timelines of their presence across different cultures globally, in many cases, it is challenging to identify cultures that maintained the continuity of those traditions.
• For instance, according to some researchers, psilocybin mushrooms were already used in 10,000 BCE. Murals discovered in northern Australia show mushrooms and psychedelic paintings. However, it doesn't seem that the tradition survived in the area.

 

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• Similarly, the oldest evidence of the use of yopo, a snuff containing 5-MEO-DMT made from the seeds of the Yopo tree that grows in the Caribean and South America, is from 4,000 BCE. Yopo paraphernalia from the time are from Argentina, though, while the tradition is currently alive among "tribes of the Orinoco basin in Colombia, Venezuela, and the southern Brazilian Amazon."
• Finally, it is challenging to pinpoint how and when cultures that originally used psychedelic plants on specific terrains (e.g., pre-Columbian cultures in Mesoamerica) passed the traditions to their successors. For the purpose of this report, we assumed that there has been a continuity of the tradition if the plant or mushroom is still used in the same area and/or by the culture linked to the ancient one.

Native Americans in Mexico and the US - Peyote

• Based on the discovery of ancient specimens of the cactus Lophophora williamsii in Texas, researchers speculate that peyote was already used by indigenous people in North America 5,700 years ago. 

Mexico

• Peyote traditions were preserved both in Mexico and the US. The Mexican tradition has a longer history, with the word "peyote" coming from Nahuatl (an Aztec language). According to research, numerous pre-Columbian cultures used the plant in the religious context, including the Aztecs and Maya. The artifacts related to those rituals—such as deer scapula rattles—were discovered along with traces of peyote, dating back thousands of years.
• In the 16th century, Fray Bernardino de Sahagún described the use of peyote in the following words, "It is a delicacy often enjoyed by the Chichimeca, for it is sustaining and spurs them to fight with no thought of fear, thirst, or hunger, and they say that it protects them from all danger."
• The Wixarika, also known as Huicholes, are particularly recognized for the later use of peyote (until today). With intensifying pressures from the Spanish in the 17th century, their practices involving peyote were stigmatized, forcing them to flee to the mountains. The colonists branded them as "the work of the devil," also comparing the rituals to witchcraft and cannibalism. However, it was increasingly difficult to contain them, given that Spanish people also started using peyote and new ceremonies emerged, blending Christianity with Wixarika rituals. Eventually, peyote rituals were banned in 1620, and participating in them could be punished by death.
• In contrast to the Spanish perception, the Huicholes saw peyote ceremonies as a way to communicate with gods. The image below presents a 19th-century figure of the god of peyote.
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• Wixarika people are among the tribes credited with preserving the peyote tradition. They currently "live in central northwest Mexico, in the Sierra Madre Occidental Mountains." Their most sacred ritual is the annual pilgrimage to the Wirikuta dessert to collect peyote, during which the cactus is "hunted" with arrows (as the tribe associates it with the spirit of the deer). It is undertaken to "return to the source of all life and heal oneself."
• Other peyote ceremonies usually take place at night, within the symbolism of the circle of death and rebirth, which is also common to Euro-American shamanic traditions.
• It is worth noting that the Huicholes tend to view peyote as all-powerful, a perspective shared by many Mexican people. According to one healer from the tribe, "Peyote is everything; it is the crossing of the souls; it is everything that is. Without peyote, nothing would exist."
• In more laic terms, according to WebMD, "Among certain indigenous populations across the Americas, peyote is believed to have medical properties. It’s been said to aid in the treatment of everything from toothaches to diabetes."
• While harvesting and using peyote is illegal in Mexico, there is a religious exemption for the Wixarika people. The legislation actually aims to protect the Huicholes and their tradition, as booming peyote tourism endangers the plant.

US

• In the US, tribes have been using peyote for thousands of years during all-night prayer ceremonies. In the 1800s, the structure was formalized with the creation of the Native American Church (NAC) that exists until today.

 

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• Importantly, while peyote is illegal in the US, US law allows its use during the ritual through the 1994 amendment to the American Indian Religious Freedom Act.
• Different Native American tribes do not view peyote as a drug but as a medicine used for healing. Interestingly, while the word "peyote" originates from the Nahuatl language, the Sioux word for medicine is "pejuta."
• The history of use before the formation of NAC is unknown. However, according to accounts by Native Americans, peyote ceremonies were what gave them the strength to accept and survive the Reservation Era in the 1800s, becoming "the religion of the poorest of the poor, the conquered, the despoiled."
• Between the 1880s and 1930s, there were attempts to ban Native American peyote rituals. The rationale behind the movement, explained by Zitkála-Šá from the Yankton Dakota Sioux Tribe, who was strongly against NAC, was as follows, "Believing that peyote is the comforter sent by God, they reject the teachings of the Church. Believing that peyote reveals the secret thoughts of man and gives superhuman knowledge of the contents of books, they deprecate the necessity of schools. Believing peyote a cure-all for every human ailment, they ignore the advice and aid of physicians. Attending the weekly peyote meetings, they waste time, strength, and money, consequently neglecting their homes and farms."
• Presently, researchers acknowledge that the primary uses of peyote in Native American tribes are healing and strengthening the community. Furthermore, the National Council of Native American Churches (NCNAC) states that the use of peyote reinforces religious values and helps overcome alcohol and drug addictions. It also emphasizes rich symbolism associated with those ceremonies, expressed through songs and art.

Ethnic Groups of the Andes - San Pedro

• The first evidence of San Pedro use is from 6,800-6,200 BCE. "Fossil remains of the cactus" dating to this period were found in "the Guitarrero cave of the Callejón de Huaylas valley" in Peru.
• Further discoveries link the use of the plant to the Chavin culture. They include stone engravings, textiles, and ceramics from around 1,300 BCE, clearly suggesting that the rituals around consumption had already formed by that time. Similar evidence was found for other pre-Columbian cultures, including Nazca, Cupinsque, Chimú, Lambayeque, and Moche.
• Some interpretations of the discoveries link early San Pedro rituals to prayers to control the supply of water, which was the primary concern for these cultures, as well as a symbol of power.
• It is worth noting that the plant's primary name among the indigenous cultures is "huachuma," which is a Quechua term for "removing the head." However, like other rituals around plants with psychedelic properties, the ones involving the use of the cactus were ostracized during colonization. The ceremonies were forced into hiding and blended with Christian symbolism.
• Calling the plant "San Pedro" is a testament to that. Local people likened it to Saint Peter, who holds the keys to heaven, believing that "huachuma" is "the gate to the spiritual realm" and a way "to achieve heaven on Earth."
• Currently, San Pedro is used in a traditional context by ethnic groups living in the Peruvian (and Ecuadorian) Andes, including the Quechua people. Its primary purposes include protecting families, diagnosing illnesses, and healing them.

 

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• The San Pedro ritual is known as "mesa." According to research by Carod-Artal and Vázquez-Cabrera, it has to follow highly specific rules, which include "'raise or sniff tobacco with alcohol, ingest San Pedro, pinpoint the diseases, cleanse the evil, and 'florecer' (flourish) the sick person." It takes place on Tuesday or Friday mornings, as those days are sacred in Andean beliefs.
• San Pedro is legal in Peru. Along with ayahuasca and coca leaves, it is considered a traditional medicine.

The Mazatecs and Other Mexican Cultures - Psilocybin Mushrooms

• The use of psilocybin mushrooms in the Valley of Mexico and the rest of Central America goes back to 3,500 BCE. They were a part of sacred traditions among the Maya, Aztecs, Huastec, Totonac, Mazatec, and Mixtec, according to the evidence such as mushroom grinding stones and sculptures depicting gods holding mushrooms.
• In the Aztec culture, the word for mushrooms was "teonanatacl," which can be translated as "god's flesh." They were used in healing and religious practices, celebrations, and festivals.
• Overall, in Mesoamerica, mushroom rituals were led by healers, who were not only supposed to cure illnesses but also predict the future and find stolen property, among others.
• Similar to the plants described above, the Spanish missionaries in the 1500s attempted to destroy the traditions around psilocybin mushrooms, as well as any evidence of their use. However, also in the 16th century, Fray Bernardino de Sahagún described their use: "They are used as medicine for fever and gout. No more than two or three should be eaten. Those who eat them see visions and feel fluttering of the heart; the visions they see are sometimes frightening and sometimes humorous. Those few who eat them in excess are driven to lust."
• Due to the pressures from the colonists, there are no accounts of how the mushrooms were used post-16th century. Bernardino de Sahagún called them "teonanatacl," and the surrounding taboo was so powerful that the researchers weren't sure what he referred to, hypothesizing that he might have described peyote.
• In the 20th century and beyond, the Mazatecs became particularly famous for their work with mushrooms, thanks to Gordon Wasson's article in Life Magazine, "In Search of a Magic Mushroom." He traveled to Oaxaca, Mexico, and participated in a sacred mushroom ritual, "velada," led by a well-known Mezatec healer Maria Sabina. He was one of the first Westerners to participate in such a ceremony.

 

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• According to Wasson's account, the tribe used mushrooms "in a particular therapeutic way, not as a cure but rather as a way of determining 'what led to the illness and whether the patient will live or die, and what should be done to hasten recovery.' For example, by ingesting the mushrooms, curanderos reportedly might learn the location of wild herbs that they could find and apply to their patients." They were also used for divination-related purposes.
• At the same time, Maria Sabina was quoted saying, "The ninos santos (Psilocybe Mexicana) heal. They lower fevers, cure colds, and give freedom from toothaches. They pull the evil spirits out of the body or free the spirit of the sick," which suggests that the significance of psilocybin mushrooms for Mexican indigenous people hasn't changed throughout the years.
• It is worth noting that Wasson's article (published in 1957) inspired some of the most important psychedelic research. Not long after, Timothy Leary founded the Harvard Psilocybin Institute. Also, in the 1960s, Wasson traveled to Oaxaca again with Albert Hofmann, who was the first person to synthesize LSD.
• The Mazatecs are among the Mexican tribes that still use psilocybin mushrooms. Other tribes include Mixe, Zapotec, Chatin, Totonac, Matlazine, and Nahuatl.
• While psilocybin is illegal in Mexico, traditional communities are unofficially allowed to use and cultivate psilocybin mushrooms. These informal exceptions are based on the United Nations' Vienna Convention from 1971, which exempts "the sacramental use of plant medicines" from its anti-drug policies.

Research Strategy

Key Takeaways

• An international study led by researchers from the University of British Columbia suggests that repeated microdosing of psychedelics may be beneficial for those struggling with mental health conditions such as depression and anxiety. 57.4% of microdosing respondents reported decreased anxiety.
• This study of 1,102 participants examines subjective experiences of microdosing psychedelic compounds to improve mental health or reduce/cease substance use. Results from the study are as follows: 44% of participants perceived that their mental health was "much better" and 35.8% perceived that their mental health was "somewhat better" after microdosing.
• The main objective of a study published in Psychopharmacology was to explore the "cognitive-enhancing potential" of psychedelic microdosing in healthy adults. Results from the study found improvements in "convergent and divergent thinking performance" after a non-blinded microdose. Fluid intelligence, however, remained unaffected.

Introduction

The University Of British Columbia (2021)

• Researchers from the University of British Colombia collected cross-sectional data for an international study on microdosing between November 2019 – July 2020 from self-selected respondents recruited via "media related to psychedelic use such as podcasts research conference presentations."

 

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• The study found that repeated microdosing of psychedelics may be beneficial for those struggling with mental health conditions such as depression and anxiety.

 

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• The substance most commonly used in this sample was psilocybin (85%).
• The authors of the study sought to contribute to the literature on microdosing by further characterizing microdosing practices. Their work included a comprehensive assessment of the practice of stacking (combing microdoses of psychedelics with other substances such as lion's mane, mushrooms, cacao, etc).
• Dr. Zach Walsh, psychology professor at the University of British Columbia believes that the findings have been promising, but more studies are required, "These cross-sectional findings are promising and highlight the need for further investigation to better determine the impacts of factors like dosage and stacking."
• The study can be found here.

Psychopharmacology — Mental Health (February 2020)

• This study of 1,102 participants examines the subjective experiences of psychedelic microdosing to improve mental health or reduce/cease substance use.
• The average age of the participants of the study was 33, and 57% of respondents have been at some point in their life diagnosed with a mental health condition.
• Results from the study are as follows: 44% of participants perceived that their mental health was "much better" and 35.8% perceived that their mental health was "somewhat better" after microdosing.
• Only 1.3% of participants indicated that their mental health was "somewhat worse", and 0.2% said that it was "much worse".
• There are several limitations to the study limiting the inference from the findings, however, including factors such as the placebo effect and lifestyle changes.
• The study can be found here.

Psychopharmacology — Creativity (October 2018)

• The main objective of this study was to explore the "cognitive-enhancing potential" of psychedelic microdosing in healthy adults. The authors also hoped that the findings would stimulate further research on the beneficial effects of microdosing psychedelics.
• The study examined the effects of microdosing psychedelic truffles on two creativity-related problem-solving tasks during an event organized by the Psychedelic Society of the Netherlands; out of 80 attendees at the event, 38 volunteered for the experiment.
• Results from the study found improvements in "convergent and divergent thinking performance" after a non-blinded microdose. Fluid intelligence remained unaffected.
• However, there are limitations to the study. The experiment was carried out "in the field;" while this allows for the benefit of studying the effects of microdosing more "naturally. This also has the disadvantage of allowing less "experimental control" than in a lab setting.
• The study can be found here.

ScienceDirect (August 2022)

• This paper represents an analysis of 44 studies on the practice of microdosing. The authors of the study are Vince Polito from the School of Psychological Sciences, at Macquarie University and Paul Liknaitzky, at Monash University.
• The research team has provided evidence to suggest that psychedelic microdosing can influence the perception of pain, subjective awareness, and the perception of time, among others.

 

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• They also found emerging evidence of possible improvements in substance abuse disorders (SUDs), mental health, and cognitive functioning, which corroborates the findings of other studies. However, researchers also noted that so far, the available evidence largely focuses on acute effects, so further research into the topic is needed.
• The study can be found here.

Research Strategy

Key Takeaways

• In 1949, Nick Bercel and Max Rinkel, two American psychiatrists, brought LSD into the U.S. to start testing it. The 1950s, 60s, and 70s were the most productive decades in the 20th century for psychedelic research.
• Towards the end of the 1960s, the U.S. government tightened the war on drugs and in 1970, introduced the Controlled Substances Act (CSA) which deemed LSD, DMT, mescaline, and psilocybin illegal. The act stopped all government-led psychedelic research, and this ban continued for the next three decades.
• Proponents of the medical use of psychedelic drugs believe that research was banned mainly because of Richard Nixon's 'War on Drugs.' He declared drug abuse public enemy number one.
• In 1962, due to the thalidomide tragedy, the Kefauver-Harris Drug Amendments to the Federal FD&C Act, referred to as the Drug Amendments of 1962, were signed into law. This tightened the regulation of pharmaceutical research.
•  Increased advocacy and support from key organizations, prominent individuals, and academic research groups in respected universities have shifted and increased public attention to psychedelic therapies, increasing their credibility.

Introduction

A Historical Context

• In 1949, Nick Bercel and Max Rinkel, two American psychiatrists, brought LSD into the U.S. to start testing it. The 1950s, 60s, and 70s were the most productive decades in the 20th century for psychedelic research.

• Many LSD studies were conducted to determine its possible uses for psychotherapy and the impacts on issues like time perception, metabolism, and its potential as a tool for fighting addiction.
• Other substances were also examined. For instance, from 1960-1962, Timothy Leary and Richard Alpert (later known as Ram Dass) gave psilocybin, mescaline, and LSD to students to study their effects through the Harvard Psilocybin Project. However, in 1963, they both had to leave Harvard; Leary's contract expired, and he wasn't interested in teaching, while Alpert was fired for giving psychedelics to undergraduate students without permission.
• Towards the end of the 1960s, the U.S. government tightened the war on drugs and in 1970, introduced the Controlled Substances Act (CSA) which deemed LSD, DMT, mescaline, and psilocybin illegal. The act stopped all government-led psychedelic research, and this ban continued for the next three decades.
• As seen on the chart below, in those 30 years, almost no scientific papers on psychedelics were published, apart from a few review and commentary articles, as well as reports from studies on animals.

 

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Key Reasons Why Medical Research on Psychedelics was Banned

1. President Nixon's 'War on Drugs'

• Proponents of the medical use of psychedelic drugs believe that research was banned mainly because of Richard Nixon's 'War on Drugs.' He declared drug abuse public enemy number one.

• President Richard Nixon's administration cracked down on psychoactive drugs as part of the broader political reaction against the 1960s' liberation movements.
• Timothy Leary, a Harvard University psychologist, had re-established himself as the “high priest” of psychedelic culture, and Nixon labeled him as the “most dangerous man in America.”
• Leary's “turn on, tune in, drop out” mantra was identified as a clear threat to the materialist, consumerist mindset and the corporate establishment.
•  Public hysteria and politics surrounding illegal drugs associated psychedelics with the anti-war and counterculture movements, creating an image of moral decline and exaggerating the effects of these substances.
• In 1970, LSD and other psychedelic drugs were included in Schedule I substances by the CSA. Schedule I substances are those that have no accepted medical use and create the potential for dependence and harm. They also lack the accepted safety for use under medical supervision. This classification came after the UN Convention on Drugs' inclusion of these drugs in Schedule I in 1967.
• This scheduling banned the clinical and medical research on psychedelics for around 40 years. Despite the public health benefits, the CSA greatly restricted research on substances placed in Schedule 1.
• Therefore, under federal law, research on psychedelic drugs was subject to criminal penalties.
• According to the report by Drug Science, the War on Drugs had significant negative effects on science and healthcare, not just in relation to psychedelics. These include restrictions on biomedical research funding, stigmatization of psychedelic research, more bureaucracy around research approval, and "limitations on fundamental neurobiology research," among others.

 

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2. Tighter Regulation of Pharmaceutical Research

• In 1962, due to the thalidomide tragedy, the Kefauver-Harris Drug Amendments to the Federal FD&C Act, referred to as the Drug Amendments of 1962, were signed into law.
• This tightened the regulation of pharmaceutical research. 
• This strengthened the FDA's legal controls on the investigation of new chemical substances in humans.

•  Informed consent of patients prior to their participation in clinical trials was not a requirement.
•  Adverse drug reaction reports were not required by the FDA.
•  Good manufacturing practices were not a formality.
• This was part of a broader re-assessment of the loose standards that were being applied to all types of drug research at the time.
• The 1962 amendments introduced the efficacy and safety requirements that had to be met during clinical drug research, and studies conducted with LSD in the 60s were unable to fulfill these requirements.
• These policies affected clinical research on hallucinogens like LSD since their testing procedures were deemed to be unethical. At the start of U.S. sample distribution, there was a limited history of psychedelic research, and psychiatrists mostly tested the drugs on any patient group that interested them.
• This strict regulation and ban eventually led to the decline in psychedelic research.

Factors that Led to Relaxing the Restrictions

•  Increased advocacy and support from key organizations, prominent individuals, and academic research groups in respected universities have shifted and increased public attention to psychedelic therapies, raising their credibility.

• With the established and strict regulation of pharmaceutical research, researchers who follow the correct protocols and prove that their research meets all the requirements are getting approvals from the Drug Enforcement Agency (DEA) and the U.S. Food and Drug Administration (FDA).
• Also, recent coverage of psychedelic research in mainstream media has been positive, and this has increased political and public interest in the topic while changing the overall perception of psychedelics.

Research Strategy

Key Takeaways

• On March 3, 2022, the state of Georgia proposed the creation of a five-member committee that would conduct a "study of the conditions, needs, issues, and problems" associated with using psilocybin-assisted therapy in treating PTSD or depression in veterans.
• On June 18, 2021, Texas passed a bill allowing the Department of State Health Services to conduct a study on the therapeutic efficacy of certain psychedelics, including ketamine, MDMA, and psilocybin, for the treatment of certain mental health issues and medical conditions, including migraines, anxiety, PTSD, depression, chronic pain, and bipolar disorder.
• A bill introduced in January 2022 in Oklahoma proposes the development of a defined route for licensed physicians and academic medical centers in Oklahoma to acquire certification that enables them to carry out clinical trials using psilocybin. This legislation requires that "only veterans aged 18 or older suffering from various forms of mental illness may participate in the clinical trials."

Introduction

Regulations That Govern Psychedelic Research Across the US States

1. Pennsylvania

• On October 12, 2021, the state of Pennsylvania introduced the legislation, i.e., the Public Health Benefits of Psilocybin Act (HB 1959), to promote research and clinical studies regarding psilocybin and psilocybin-assisted therapy in order to discover innovative ways of utilizing psilocybin mushrooms to treat PTSD, including other mental health conditions in veterans, first responders, and their families. It also allowed cultivating limited amounts for research purposes.
• Links to the entire legislation and house co-sponsorship memoranda are available here and here, respectively.

2. Georgia

• On March 3, 2022, the state of Georgia proposed the creation of a five-member committee that would conduct a "study of the conditions, needs, issues, and problems" associated with using psilocybin-assisted therapy in treating PTSD or depression in veterans. In addition, it would also look for ways of treating people struggling with addiction. The committee has until December 1, 2022, to come up with action or legislation they deem fit to leverage psilocybin-assisted therapy in treating veterans.
• A link to the entire legislation is available here.

3. New York

• The state of New York, on June 1, 2021, introduced a bill that would see it establishing a public psychedelic research institute and a psychedelic substances therapeutic research program. In collaboration with another bill introduced on December 13, 2021, the state proposed the development of psilocybin service centers to offer innovative treatments of various health problems, such as depression, PTSD, anxiety, and others, affecting veterans, police officers, firefighters, and EMS workers.
• The links to June 1, 2021, and December 13, 2021, proposed bills are found here and here, respectively.

4. Texas

• On June 18, 2021, Texas passed a bill allowing the Department of State Health Services to conduct a study on the therapeutic efficacy of certain psychedelics, including ketamine, MDMA, and psilocybin, for the treatment of certain mental health issues and medical conditions, including migraines, anxiety, PTSD, depression, chronic pain, and bipolar disorder. The working group (the department) will evaluate and compare the effectiveness of these psychedelics-assisted therapies with current treatments. They are expected to submit their findings by December 1, 2022, and the bill will expire on September 1, 2023.
• The link to the entire bill can be found here.

5. Utah

• On March 22, 2022, Utah passed a bill that created the Mental Illness Psychotherapy Drug Task Force to conduct research and garner evidence on any psychotherapy drug that, when used, "may enhance psychotherapy when treating a mental illness.” The task force is expected to submit its findings by October 31, 2022.
• The link to the entire bill is available here.

6. Oklahoma

• This year, 2022, in January, two Oklahoma representatives, i.e., Logan Phillips (R) and Daniel Pae (R), proposed two bills that "would promote scientific research into psilocybin-assisted therapy and help foster new clinical trials."
• Philip's bill proposes the development of a defined route for licensed physicians and academic medical centers in Oklahoma to acquire certification that enables them to carry out clinical trials using psilocybin. This legislation requires that "only veterans aged 18 or older suffering from various forms of mental illness may participate in the clinical trials."
• Pae's bill proposes increasing psilocybin research in Oklahoma, but unlike Philip's bill, "it allows anyone over 18 suffering from a list of specified conditions to participate in clinical trials."
• The links to Philip's and Pae's entire bills are available here and here, respectively.

7. Connecticut

• On June 7, 2021, Connecticut passed a law that allowed the Department of Mental Health and Addiction Services to create a working group to conduct a study and establish the health benefits of psilocybin. Also, the study allowed the group to determine if someone experiences physical or mental well-being after using psilocybin under the supervision of a healthcare provider. The findings of the research were submitted by January 1, 2022.
• On May 7, 2022, the state passed a bill to adjust funds allocated to psychedelic-assisted therapy pilot programs that involve administering psilocybin and MDMA treatments to veterans, retired first responders, and others under the supervision of an approved federal FDA treatment site.
• The links to June 7, 2021, and May 7, 2022, bills are available here and here, respectively.

8. Massachusetts

• On March 29, 2021, the state of Massachusetts proposed a bill to form "an interagency task force to study the public health and social justice implications of legalizing the possession, consumption, transportation, and distribution of naturally cultivated entheogenic plants and fungi."
• The link to the entire bill is available here.

A Mapping of Psychedelic Drug Policy Reform Across the US States

 

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Research Strategy

Key Takeaways

• In 2018, 7.4% of Spanish long-term ayahuasca users reported high cholesterol or blood pressure. The percentage rose to 18-20% among the general Spanish population.
• In a 2015 study, brain scans showed differences in medial parts of the brain between ayahuasca users and the control group. Specifically, cortical thickness (CT) in the anterior cingulate cortex and the posterior cingulate cortex differed between the two groups. These changes have been linked to increased openness and specific elements of spirituality among ayahuasca users. Furthermore, the researchers associated the thinning in the posterior cingulate cortex (PCC) specifically with decreased "prior maladaptive behaviors such as drug abuse."
• An epidemiological study of 29 MDMA users "who averaged 3.6 tablets per week for 6.1 years" found that 28% developed valvular heart disease (VHD), compared to none among their non-user matches.

Introduction

Research on Long-Term Psychedelic Use

Ayahuasca and Public Health

• A study "Ayahuasca Public Health," conducted in 2018 and published in 2019, assessed the health status of 380 long-term, regular ayahuasca users in Spain. The mean age of participants was 44, 47% of them were female, and 38% belonged to the Santo Daime church, a Brazilian religious group with the tradition of drinking ayahuasca. The results were compared with the available data on non-users.
• The study was a collaboration between researchers from Brazil and Spain. One of the involved institutions was the International Center for Ethnobotanical Education, Research, and Services (ICEERS).
• The study used a questionnaire with indicators taken from psychometric questionnaires and health surveys. Health measures included self-perceived health, body mass index (BMI), chronic diseases, physical limitation, sleep problems, cholesterol, blood pressure, medical visits, and use of prescription drugs.
• Among the notable results that may be associated with ayahuasca use, 7.4% of users reported high cholesterol or blood pressure. The percentage rose to 18-20% among the general population.
• Furthermore, participants in ayahuasca ceremonies do not use healthcare services as often as the general population. For instance, 52.5% of surveyed ayahuasca users visited a medical professional in the past six months, compared to 86.8% of the general Spanish population. At the same time, 56% of users stated that they were reducing their consumption of prescription medicines.
• Also, 14% of participants reported having a chronic disease, compared to 60% of the overall population. The differences were significant among each age group, though it might have been influenced by the sample size of selected age groups among participants.
• Overall, 96.6% of ayahuasca users had a positive perception of their health, compared to 74% of the Spanish population.
• Since access to the article on Academia may be restricted, the PDF can also be viewed here.

Ayahuasca and Public Health II

• The second part of the study, "Ayahuasca and Public Health II," published in the Journal of Psychoactive Drugs in December 2021, assessed the health of 377 participants of ayahuasca ceremonies in the Netherlands and compared them against "normative Dutch data." The mean age of participants, of whom 50.1% were women, was 48.8 years. The assessment was again conducted with a questionnaire that included selected health indicators, among others.
• 58% of surveyed ayahuasca users were participating in ceremonies for over five years, while 30% took part in over 100 such rituals.
• The work is a collaboration between researchers from the Netherlands, Brazil, and Spain (the full list of names with affiliations is available here) with the objective to inform public policies. ICEERS was also involved.
• It's important to note that the full study is paywalled. However, the abstract and the third-party article describing the research include the key results. Since it is the most recent full study available, we decided to still present it.
• According to the results, one key effect of regularly drinking ayahuasca is a lifestyle change. 74% of participants met Dutch exercise guidelines. They also ate healthier food, including more fruits, vegetables, and legumes.
• This leads to better health outcomes, i.e., lower odds of having high blood pressure, chronic disease, or diabetes. Unfortunately, the quantitative difference is not available.
• For additional context, though it is not specific to physical health outcomes, those who attended 100+ ceremonies were more likely to use "problem-solving coping strategies," while those who attended 3-10, avoidant coping strategies.

Long-Term Use of Psychedelic Drugs

• A 2015 study assessed the changes in the brain and personality of 22 Santo Daime church members in Spain, who had been using ayahuasca about 50 times per year for over five years (on average). They were compared against a control group o 22.
• The methods included an interview with a clinical psychologist to eliminate the possibility of neurological or psychiatric disorder skewing the results, IQ test, and 3-T brain scans. Additionally, personality, psychopathological, and neurobiological tests were used.
• The study was a joint effort between scientists from Spain and Brazil, funded by the Spanish Government. ICEERS was also involved, like in the studies described above. However, non-ICEERS institutions and individuals were different, and the studies are not related.
• The results showed differences in medial parts of the brain between ayahuasca users and the control group. Specifically, cortical thickness (CT) in the anterior cingulate cortex and the posterior cingulate cortex differed between the two groups. These changes have been linked to increased openness and specific elements of spirituality.

 

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• Furthermore, the researchers associated the thinning in the posterior cingulate cortex (PCC) specifically with decreased "prior maladaptive behaviors such as drug abuse."
• The brain scans of Santo Daime members displayed "greater CT in the anterior brain regions involved with attention and executive control," suggesting that ayahuasca use may enhance executive function. The authors of the study cited older research, which noted that regular ayahuasca users perform significantly better on neuropsychological tests.
• The study concluded that further research is needed, but it is likely that the long-term use of psychedelics leads to changes in brain tissue.

Microdosing and Valvular Heart Disease (VHD)

• While not a full study or research paper, a 2022 article published by Dr. Kelan Thomas from the University of California College of Pharmacy focuses on a particular physical health risk related to microdosing, which is valvular heart disease (VHD). It is included due to presenting a unique perspective.
• The condition "is characterized by damage to the heart valves, which control the flow of blood into and away from the heart. VHD can cause shortness of breath, weakness, and sudden cardiac death," as per the article.
• The argument is not based on a study, but the author calls it "compelling theoretical evidence."
• According to the article, the link between medications with strong serotonin 2B receptor (5HT2B) binding affinity and VHD is not only well-known but even acknowledged by FDA.
• Furthermore, one epidemiological study on 29 MDMA users "who averaged 3.6 tablets per week for 6.1 years" found that 28% developed VHD, compared to none among their non-user matches (based on age and gender).
• While none similar studies were conducted for frequently microdosed psychedelics, such as LSD and psilocybin, their binding affinity for the receptor is stronger, so the risk is likely higher.

Additional Findings

• A 2020 summary of existing research on the long-term effects of psychedelics focuses exclusively on mental health outcomes. Furthermore, the available studies it references strongly suggest that the vast majority of research on the topic revolves around the long-term outcomes of a single use.
• Additionally, there are sources that directly state that the long-term effects of psilocybin on brain function haven't been studied, while outcomes of continuously using peyote have only been examined briefly and may not be relevant outside of the Native American context.
• A 2018 paper published in Neuroscience & Biobehavioral Reviews, "Serotonergic psychedelics and personality: A systematic review of contemporary research," explains how 5-HT2A receptor expression influences personality changes in both long-term and acute use. However, we were only able to access the abstract due to the paywall.
• Also, for additional context on the impact of classic psychedelics on the body, a 2021 research paper analyzes the results of the National Survey on Drug Use and Health to determine the correlation between lifetime (as opposed to long-term) use of psychedelics and cardiometabolic diseases. It notes that previous research showed that lifetime classic psychedelic use is linked to lower risks of obesity and hypertension, while the current paper associates it with decreased odds of diabetes and heart disease.

 

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Research Strategy

Key Takeaways

• VETS was started in 2019 by Marcus Capone after he became medically retired from multiple combat deployments as a US Navy SEAL.
• Reason For Hope was named in memory of the co-founder Brett Waters’ mother, Sherrie Hope Waters, who died by suicide in 2018.
• Heroic Hearts Project provides safe and supervised access to psychedelic treatments to veterans suffering from military trauma, so they can recover and thrive.

Introduction

Organizations and Programs Focusing on Treating PTSD With Psychedelics

Multidisciplinary Association for Psychedelic Studies

• The Multidisciplinary Association for Psychedelic Studies (MAPS) is a not-for-profit research and educational organization.
• It was founded in 1986 by Rick Doblin in the US. He wanted to use the organization to "continue researching the healing potential of MDMA and other psychedelics."

 

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• MAPS uses research, education, and advocacy to change how people talk about, think about, and consume psychedelics.
• The organization is a clinical trial sponsor striving to get approval for the use of 3,4-methylenedioxymethamphetamine (MDMA) to treat patients with PTSD.
• MAPS is also conducting clinical studies on the use of MDMA to alleviate PTSD in veterans.

The Center for Psychedelic Psychotherapy and Trauma Research

• The Center for Psychedelic Psychotherapy and Trauma Research was started in September 2020 at the Icahn School of Medicine at Mount Sinai (Mount Sinai) and the James J. Peters Department of Veterans Affairs Medical Center (the Bronx VA),

• It assesses the therapeutic potential of psychedelic compounds for PTSD.
• It conducts clinical trials on the current use of psychedelics in trauma survivors to understand how they work.
• The center also offers education and training to medical residents, therapists, and trainees to prepare them for working with psychedelic therapies.

Heroic Hearts Project

• Heroic Hearts Project is a nonprofit founded in 2017 in the US by Jesse Gould, a war veteran who was deployed as an Army Ranger in Afghanistan three times.
• It provides safe and supervised access to psychedelic treatments to veterans suffering from military trauma, so they can recover and thrive.

 

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• The organization primarily works with ayahuasca retreat centers because they have great results in healing PTSD.
• Heroic Hearts Project uses research, education, and advocacy to counter the stigma people have about psychedelics and help change laws that limit access to psychedelics as therapeutics.

Veterans Exploring Treatment Solutions (VETS)

• VETS was founded in 2019 by Marcus Capone after he became medically retired from multiple combat deployments as a US Navy SEAL.

 

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• It provides funding for Special Operations veterans to receive coaching and access to psychedelic therapies, such as ketamine, psilocybin, MDMA, ibogaine, 5-MeO-DMT, and ayahuasca, for PTSD.
• It also offers educational resources for military members about the risks and benefits of psychedelic therapies to help end the veteran suicide epidemic.
• VETS advocates for dissolving stigmas associated with trauma and psychedelic therapies.
• It also provides grants for hundreds of US Special Forces veterans to receive psychedelic-assisted therapy treatment outside the US.

Center for Psychedelic Research & Therapy

• The Center for Psychedelic Research and Therapy at Dell Medical School at The University of Texas at Austin was launched in December 2021.

• Its goal is to advocate for the use of psychedelics to treat mental health disorders through impactful clinical research.
• The center also strives to use psychedelic-assisted psychotherapy and research to improve the health of those suffering from PTSD, especially military veterans and adults affected by early childhood trauma.

Reason For Hope

• Reason For Hope was named in memory of the co-founder Brett Waters’ mother, Sherrie Hope Waters, who died by suicide in 2018.

• It advocates for psychedelics like psilocybin mushrooms to be widely available for treating PTSD to "prevent deaths of despair."
• The organization is currently "focused on establishing MDMA- and psilocybin-assisted therapy expanded access pilot programs for people who can't afford to wait for FDA approval."

Research Strategy