Research Strategy:

• We directed our research in search of human clinical studies (observational and clinical trials). Using PubMed and Clinicaltrials.gov, we used the search terms CBD and autoimmune disease, CBD and hormone imbalance, CBD and metabolic dysfunctional disease, to narrow down the therapeutic role of CBD in the aforementioned diseases. We also used CBD nomenclature substitutes to identify different clinical studies published in high-impact factor journals.
• CBD's role in diseases associated with hormone dysfunction and metabolic disease was not directly available (upon screening through PubMed.) However, devising customized search algorithms using specific disease names might be intuitive in the future. Should the client need this information, it can be addressed as a separate request in the future.
• Given the time crunch of 3 hours, it was nearly impossible to conduct a quick systematic review on the three domains (autoimmune disease, hormone imbalance, and metabolic dysfunctional disease). We focused our search on diseases that have a high degree of accumulated evidence such as (i) auto-immune disorders and (ii) diseases of inflammatory origin. In addition, we worked on it for an extra two hours (free-of-cost) to address the therapeutic role of CBD in the aforementioned conditions.
• We compiled a list of studies that demonstrated the therapeutic role in the treatment of systemic diseases, in addition to presenting the main findings in the attached google spreadsheet.
• As per the client need of educating patients, we felt it is necessary to cover additional topics outlined below:
• A comprehensive overview of the therapeutic potential of CBD in various systemic diseases.
• Recent evidence surrounding CBD use — licensed drugs for use in specific medical conditions.
• The approved list of indications for CBD (from the legislative aspect supported by the scientific data)
• Potential side effects and related complications
• Contraindications for CBD use.

Pharmacology of Cannabinoids (CBD):

• The Cannabinoid receptors include CB1 and CB2 expressed in the brain and on the surface of immune cells respectively. In fact, both CB1 and CB2 receptors are present on the immune cells, which indicates that CBD plays an important role in the regulation of the immune system.

Nomenclature associated with CBD:

• CBD is also known as cannabis/cannabinoid, or endocannabinoid, or marijuana or THC.

•  THC (Tetrahydrocannabinol): refers to the naturally occurring (-)-trans isomer of delta-9-tetrahydrocannabinol from the cannabis plant (Cannabis sativa L).
•  Dronabinol: international non-proprietary name (INN) for (-)-trans-delta-9-tetrahydrocannabinol and is used synonymously with THC.
• Dronabinol is licensed (in the USA) for the treatment of (i) Nausea due to cancer chemotherapy, and (ii) Loss of Appetite in AIDS patients with weight loss.
•  Nabilone: a synthetic derivative of Tetrahydrocannabinol (THC). It is licensed for the treatment of nausea in chemotherapy. A quantity of 1 mg nabilone has about the same effect as 7–8 mg dronabinol.
•  Cannabidiol (CBD): It is not a cannabinoid receptor agonist, but it is the most important non-psychotropic cannabinoid found in the cannabis plant.

Recent Supporting Evidence around CBD use:

• The two recent systematic reviews (of high quality) concluded that the only evidence for medical marijuana in treating neurological disorders has been for reducing (i) the symptoms of patient-reported spasticity and (ii) central pain in Multiple Sclerosis.
• The study concluded that [i] Nabiximols (Sativex oral spray), [ii] oral cannabis extract (OCE), and [iii] synthetic tetrahydrocannabinol (THC) were effective in reducing patient-reported symptoms of Spasticity in Patients with Multiple Sclerosis. However, but OCE and synthetic THC were not effective in reducing physician-administered measures of spasticity.
• Nabiximols, OCE, and synthetic THC demonstrated an effective reduction in MS-related pain.
• Cannabinoids demonstrated to be safe and well-tolerated in humans.

Therapeutic Potential of Cannabinoids (CBD):

• Cannabinoids have demonstrated a range of therapeutic utility in the management of cancer, obesity, neurologic diseases, and for inducing immunosuppression and anti-inflammation.
• CBD has also demonstrated efficacy in the treatment of inflammatory and neoplastic dermatological conditions.  
• Various studies have demonstrated the efficacy of CBD in the treatment of (i) Nausea and Vomiting associated with cancer chemotherapy, (ii) Anorexia and Cachexia in HIV/AIDS patients, and (iii) Neuropathic pain and Spasticity in Multiple Sclerosis. The aforementioned conditions are established indications for treatment with cannabinoid medications.
• Cannabis extract which contains tetrahydrocannabinol (THC) and CBD (in a 1:1 ratio) was licensed in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis.
• Some randomized clinical trials have demonstrated efficacy in the treatment of Bladder dysfunction in MS, Tics in Tourette syndrome, and Levodopa-induced dyskinesia in Parkinson’s disease.
• The therapeutic properties of cannabinoids include anti-inflammatory, neuroprotective, analgesic, antispasmodic, antioxidant, antibiotic, anticonvulsive, antiviral, antifungal, bone stimulant, anxiolytic, antipsychotic, vasorelaxant, antidiabetic, antiproliferative, and anti-tumor.
•  Areas of therapeutic potential for cannabinoids are highlighted in the figure below (Source: Izzo et al., 2009). Figure Abbreviations: CBN, cannabinol; CBD, cannabidiol; D9-THCV, D9-tetrahydrocannabivarin; CBC, cannabichromene; CBG, cannabigerol; D9-THCA, D9-tetrahydrocannabinolic acid; TRPV1, transient receptor potential vanilloid type 1; PPARg, peroxisome proliferator-activated receptor g; ROS, reactive oxygen species; 5-HT1A, 5-hydroxytryptamine receptor subtype 1A; FAAH, fatty acid amide hydrolase. (+), direct or indirect activation; ↑, increase; ↓, decrease.
•  
  Source

Medical Marijuana Current Indications:

• According to the 2019 legislation for medical marijuana use in the state of Colorado, New Mexico, Oregon, and Rhode Island, the following conditions are indicated for its use:

• Severe pain
• Muscle spasms
• Severe nausea
• Severe Anorexia/Cachexia
• Post-traumatic stress disorder (PTSD)
• Cancer
• Seizures
• Glaucoma
• HIV/AIDS
• Autism spectrum disorder
• Amyotrophic lateral sclerosis
• Crohn’s disease
• Ulcerative colitis
• Inflammatory Bowel Disease
• Damage to the nervous tissue of the spinal cord
• Epilepsy
• Glaucoma
• Hepatitis C infection
• Hospice care
• Huntington’s disease
• Inclusion body myositis
• Inflammatory autoimmune-mediated arthritis
• Intractable nausea/vomiting
• Multiple Sclerosis
• Persistent muscle spasms, including spasms caused by multiple sclerosis
• Painful peripheral neuropathy
• Parkinson’s disease
• Agitation related to Alzheimer’s disease
• Spasmodic torticollis (cervical dystonia)
• Degenerative or pervasive Neurologic condition

Problems associated with CBD - Side Effects:

• The most common side effects include tiredness and dizziness (in more than 10% of patients).
•  Other side effects include tachycardia, orthostatic hypotension, dry mouth, reduced lacrimation, muscle relaxation, and increased appetite.
• Continued use of CBD in patients suffering from Hepatitis C, may accelerate the development of Cirrhosis.
• The CBD withdrawal symptoms are found in chronic users after abrupt cessation of CBD use. The withdrawal symptoms include uneasiness, irritability, sleeplessness, increased perspiration, and loss of appetite
• CBD use has been associated with [i] increased risk of psychosis and schizophrenia (in at-risk individuals), [ii] increasing the risk for cardiovascular diseases (including hypertension, heart failure, myocardial infarction, and stroke), and [iii] cannabinoid hyperemesis syndrome.

Contraindications:

•  Allergic reaction to components of CBD preparations
• Severe personality disorders and psychoses
•  Pregnant and breast-feeding women - because of potential developmental disorders in children
•  Pre-pubertal Adolescents children - because of inadequate data on safety/efficacy in children under the age of 18 years.
•  Elderly population - vulnerable to central nervous and cardiovascular side effects.
• Patients with severe cardiovascular diseases  
• Patients suffering from Hepatitis C  
• Patients with a history of Addictive disorders