Medical Marijuana – Myth or Magic?

Marijuana has been a controversial subject that polarizes healthcare providers and patients alike and has garnered immense attention recently for many reasons – decriminalization, legalization, medical uses, abuse as a ‘gateway’ drug, etc. Irrespective of personal opinions, it remains a mystery to primary care physicians and needs to be addressed with scientific evidence as well as subjective experience. In this themed edition of SGIM Forum we have tried to bring together a group of pioneers and experts to discuss some aspects of marijuana. But before we do that perhaps we need to establish a few basic facts about marijuana, as well the medical disorders for which it may used.

Marijuana, a mixture of the dried leaves and flowers from the plant Cannabis sativa, is the most common illegal recreational drug in the world. It can be smoked, eaten in baked goods, brewed as tea, or administered in a tablet or liquid form. Globally 3.5% of the population has used marijuana at least once. It has conventionally been labeled as a Schedule 1 drug in the US, indicating that it is a drug of addiction with no known medicinal value, on par with heroin and cocaine. In the last couple of decades, however, attention has shifted to its medicinal properties. Promoters of medical marijuana point out that the premise of labeling it as an addictive drug is based on insufficient evidence about its pharmacological properties, that the prevalence of addiction to marijuana is <10%, and that neither intoxication nor withdrawal is life threatening as opposed to alcohol, cocaine or heroin.

Of all the different cannabis compounds, tetrahydrocannbinol (THC) is the psychoactive ingredient that causes altered mood, impairment in movement, thinking, and problem solving as well as hallucinations and paranoia. Cannabidiol (CBD) is believed to have medicinal properties without psychoactive effects. It is neuroprotective and has anxiolytic, anti-convulsant, anti-inflammatory, and sedative effects. It has been suggested that the form of cannabis with a higher proportion of CBD and low amounts of THC can be prepared for use in several debilitating conditions for which traditional medications prove ineffective, though many find it challenging to promote a drug traditionally used recreationally. Current literature is inadequate and scientifically weak but case reports and case series have been described that are compelling. Research on marijuana has been difficult due to regulatory limitations. We describe a few conditions that may respond to medical marijuana when traditional treatments have been ineffective.

Multiple Sclerosis (MS) – There is definite evidence that marijuana reduces spasticity in multiple sclerosis and spasm related pain due its anti-inflammatory properties as shown in 12 trials with 1600 patients.¹ Urinary bladder symptoms, depression, constipation, insomnia, fecal incontinence and defecation urgency have also been relieved. The American National MS Society supports patients who are interested in exploring this option. Marijuana does not reduce tremors, neuropathic pain, or disease progression and may elevate the risk for cognitive impairment. An oral spray Sativex is available for prescription use.

Chronic pain syndromes – This is the most common use of medical marijuana and it can be used with negligible side effects or addiction in labor pain, migraines, arthritis, cancer pain, pain from spasticity, endometriosis, fibromyalgia etc as proven in six trials with 325 patients.¹ After robust review of existing literature, the Institute of Medicine (IOM), a highly esteemed peer institution in USA, has deemed that marijuana in any form can cause mild to moderate pain relief on par with codeine.

Cachexia/wasting syndrome – This is usually seen in patients with AIDS, cancer or advanced dementia when they have very poor appetite and consistently lose weight with failure to thrive. Several small clinical trials have demonstrated that marijuana in inhaled or oral form stimulates appetite, stops weight loss, causes weight gain, and reduces nausea more than a placebo in patients with AIDS, cancer or advanced dementia.² These effects were found to be long term. It is well tolerated usually and has low side effects. Based on this moderate evidence for marijuana, the Federal Drug Association (FDA) had approved the use of dronabinol (synthetic form of cannabis, trade name Marinol) for use in AIDS patients with weight loss.

Severe nausea and vomiting – Dronabinol and Nabilone are synthetic forms of cannabis used for intractable chemotherapy related nausea and vomiting treatment.² Dronabinol is FDA approved for this indication. According to the American Society of Clinical Oncology, however, it should not be used as a first line treatment in this situation. There are excerpts of doctors allowing patients to smoke marijuana to control nausea.

Amyotrophic Lateral Sclerosis (ALS) – Cannabis can relieve muscle spasm and pain, improve breathing by relaxing bronchial muscles, reduce drooling by inhibiting saliva, stimulate appetite and sleep, and reduce depression.³ It does not help in speech, swallowing and sexual dysfunction. Cannabis may slow down the progression of ALS, but can aggravate the already compromised respiratory system and cause death by respiratory failure. It is legally available for use in ALS in 6 states in USA. The ALS Association supports further research related to the use of cannabis for ALS but also issues a cautious approach to the use of marijuana as a drug of choice based on current evidence.

Crohn’s Disease (CD) – Due to its anti-inflammatory properties, patients with Crohn’s disease report a reduction in symptoms with marijuana as proven by a clinical trial.⁴ Crohn’s disease is one of the few diseases for which a human clinical trial has been done with cannabis. In this study, subjects were given inhaled marijuana twice daily for 8 weeks. The trial concluded that cannabis can resolve symptoms of pain and nausea, improve appetite and sleep, has minimal side effects, and is steroid sparing. However, the effects are short term and after two weeks of stopping it, all symptoms may recur.

Seizure Disorder – Twenty percent patients with epilepsy in USA smoke marijuana and report reduction in seizures, especially in intractable seizure syndromes like Dravet Syndrome, propelling an increase in demand.⁵ Large clinical trials are needed to conclusively prove its anti-convulsant efficacy.

Glaucoma – Smoking marijuana reduces pressure within the eyes of all individuals with our without glaucoma but it is short acting and no clinical trials have been done. Side effects include sedation, dry mouth, dizziness, depression, confusion, and weight gain. Eye drops have low penetration. The American Glaucoma Society position statement on the use of marijuana for glaucoma is that “although marijuana can lower the IOP, its side effects and short duration of action, coupled with a lack of evidence that its use alters the course of glaucoma, preclude recommending this drug in any form for the treatment of glaucoma at the present time.”

Post Traumatic Stress Disorder (PTSD) – Many patients with PTSD smoke marijuana to improve their sleep, appetite and depression and a single study showed reduction in nightmares. Research suggests that one of the cannabinoid chemicals may block negative memories or fear associated with the trauma in a process called reconsolidation blockage – memories that remain latent and get reawakened need to be stabilized again for them to persist, a process called reconsolidation. If reconsolidation is blocked, then there is a weakening of the original memory.

Movement Disorders and Dementia – Marijuana may ameliorate a few symptoms in Parkinson’s Disease, Huntington’s Disease, and Alzheimer’s. No large clinical trials have been reported though several are currently ongoing with Sativex spray.

Regardless of personal beliefs and outlook, it is critical that healthcare providers enhance their knowledge about marijuana as the anticipation is that it will continue to be a hot topic of discussion. My interview with Joel Stanley, CEO of C. W. Botanicals, gives a unique perspective on the growers of this plant and the barriers that they face in trying to make it available for patients with long standing chronic debilitating diseases while trying to meet all regulatory requirements.

References:

(1) Hill KP1. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA. 2015 Jun 23-30;313(24):2474-83.

(2) Whiting PF1, Wolff RF2, Deshpande S, etal. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73.

(3) Amtmann D1, Weydt P, Johnson KL, et al. Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care. 2004 Mar-Apr;21(2):95-104.

(4) Naftali T1, Bar-Lev Schleider L, et al. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1276-1280.

(5) Devinsky O1, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014 Jun;55(6):791-802.