By: Dragan M Svrakic, MD, PhD*, Patrick J Lustman, PhD*, Ashok Mallya, MD**, Taylor Andrea Lynn, PhD**, Rhonda Finney, RN**, Neda M Svrakic***
Published in Missouri Medicine, the journal of the Missouri State Medical Association, March/April 2012
* Washington University School of Medicine in St Louis
Veterans Administration Medical Center in St Louis
** Veterans Administration Medical Center in St Louis
*** University of Illinois in Champagne Urbana
Dragan M Svrakic MD PhD
VAMC St Louis
Bell Street Clinic, 915 N Grand blvd
St Louis MO 63106
Empirical and clinical studies clearly demonstrate significant adverse effects of cannabis smoking on physical and mental health as well as its interference with social and occupational functioning. These negative data far outweigh a few documented benefits for a limited set of medical indications, for which safe and effective alternative treatments are readily available. If there is any medical role for cannabinoid drugs, it lies with chemically defined compounds, not with unprocessed cannabis plant. Legalization or medical use of smoked cannabis is likely to impose significant public health risks, including an increased risk of schizophrenia, psychosis, and other forms of substance use disorders.
In recent years, there has been a strong pressure on state legislatures across the US to legalize or decriminalize use and possession of specified amounts of cannabis (figures 1 and 2) and/or to pass laws that allow smoking of crude cannabis plant (also known as marijuana, weed, Mary Jane, pot, reefers, ganja, joint and grass) for prescribed medical purposes (so called “medical marijuana”). Advocacy groups claim that smoking cannabis is a safe and effective treatment for various psychological and medical conditions, ranging from stress and anxiety to Alzheimer’s dementia and Parkison’s disease, even though cannabis is not approved for such use by the Food and Drug Administration (FDA).
Legalization of cannabis is the process of removing all legal prohibitions against it. Cannabis would then be available to the adult general population for purchase and use at will, similar to tobacco and alcohol. Decriminalization is the act of removing criminal sanctions against an act, article, or behavior. Decriminalization of cannabis means it would remain illegal, but the legal system would not prosecute a person for possession under a specified amount. Instead, the penalties would range from no penalties at all, civil fines, drug education, or drug treatment.
No state has legalized cannabis thus far. It remains a U.S. federally controlled substance, which makes possession and distribution illegal. However, at the time of this writing, 26 states in the US have passed either medical cannabis laws, cannabis decriminalization laws, or both (Figure 1). A major concern of this commentary is that both the medicinal use of smoked cannabis plant and legalization/decriminalization of cannabis are being advocated in a way that circumvents the normal testing and regulatory processes by the FDA that is otherwise required for all drugs marketed for human use in the US. By circumventing this process, advocacy groups put state legislatures and/or voters in the position to decide on proposals with a certain impact on public health and medical treatment without necessarily being qualified to understand the pertinent scientific evidence.
Taking advantage of the obscure legal status of cannabis (i.e., federally banned illicit drug but approved by local governments for medical and/or recreational purposes), businesses involving sales of cannabis are flourishing and even stock-market investments are available. For example, CannabisInvestments.com provides information on ways one can invest in hemp-related and medical marijuana products and companies. These business interest groups are ratcheting up pressure on state legislatures to decriminalize or medicalize cannabis, counting on support of millions of addicted users and politicians looking for re-election votes and unaware of the dangers of such a legislative act.
Historically, cannabis has been used in various cultures and populations as indigenous therapy for a range of medical ailments (e.g., fever, insomnia, cachexia, headache, constipation, rheumatic pain) and diseases (e.g., venereal disease, malaria). Due to its presumed medical benefits, cannabis was recognized as an official, licit drug and listed in the U.S. Pharmacopoeia in 1850. Recreational use of cannabis surged in the 1930s during the Prohibition Era. In 1937, the Marijuana Tax Act effectively thwarted all cannabis use without criminalizing its possession or use. In 1970, the Controlled Substances Act classified cannabis as schedule I illicit drugs, the most restrictive category, and made possession a federal crime.
The Drug Enforcement Agency (DEA), which administers the Controlled Substances Act, continues to support the Schedule I assignment (and FDA concurred) noting that cannabis meets the three criteria for such placement under 21 U.S.C. 812(b): (1) high potential for abuse, (2) no currently accepted medical use in the US, and (3) lack of accepted safety for use under medical supervision.
A past evaluation by several Department of Health and Human Services (HHS) agencies, including FDA, Substance Abuse and Mental Health Services Administration (SAMHSA) and National Institute for Drug Abuse (NIDA), concluded that no sound scientific studies supported medical use of marijuana and no animal or human data supported the safety or efficacy of marijuana for general medical use.1
In the public debate, cannabis has been considered a relatively benign recreational drug in comparison to opiates, stimulants, even alcohol. The favorable popular perception of cannabis presumably reflects the absence of dramatic physical signs of intoxication or withdrawal. Incidentally, cessation of cannabis use does cause withdrawal, but the severity is masked by the gradual release of delta 9 -tetrahydrocannabinol (THC), the major psychoactive ingredient in cannabis, from fat tissue (adipocytes) where it accumulates during chronic use. The process is not unlike the tapering of medication during detoxification.
The general public has not been adequately informed about recent scientific findings demonstrating major adverse effects of smoking cannabis on physical and especially mental health, the latter varying in range from cognitive dulling, brief psychotic experiences, to long-term addiction and chronic psychosis.2,3 (Figure 3)
Cannabis (here referring to smoking of cannabis plants) is the most commonly used illicit drug in the US. Data from The National Survey on Drug Use and Health 4, 5 indicate that 44% of males and 35% of females have used marijuana at least once in their life time. More recent studies suggest that regular use of marijuana is increasing. Data from National Survey on Drug Use and Health6 indicate that in persons over the age of 12, the rate of past month cannabis use and the number of users in 2009 (6.6 percent or 16.7 million) were higher compared to 2008 (6.1% or 15.2 million) and 2007 (5.8% or 14.4 million).
Since THC was first isolated and purified7 from the cannabis plant in 1965, more than 400 chemicals have been isolated, approximately 60 of which are cannabinoids, compounds that are the active agents of cannabis. Reflecting a rapidly growing interest in the therapeutic potential of cannabis, about 21 cannabinoids are currently under study by the US FDA.8
More recently, two types of cannabinoid receptors have been identified: CB1 found mostly in the central nervous system and responsible for psychoactive properties of cannabis, and CB2 found mostly in the spleen, immune tissues, and peripheral blood, and responsible for immunological and anti-inflammatory effects of cannabis.9,10 A group of endo-cannabinoids has been also identified, e.g., arachidonoylethanolamine or anandamide, as endogenous chemical modulators which mimic the actions of phytocannabinoids and activate cannabinoid receptors.10 These discoveries have led to the development of numerous CB receptor agonists and antagonists and numerous studies have tested therapeutic indications for these compounds. Medications containing natural or synthetic cannabinoids currently approved or being considered for approval for medicinal use are listed below:
Dronabinol (proprietary name Marinol), a synthetic THC, is FDA approved as an antiemetic in patients undergoing cancer chemotherapy, as an appetite stimulant for weight loss/decreased food intake in AIDS patients, and less frequently to augment analgesic treatment. Dronabinol is a Schedule III mediciation, indicating it has some potential for psychological and physical dependence.
Nabilone (proprietary name Cesamet), is a synthetic cannabinoid FDA approved for peroral treatment of nausea and vomiting in chemotherapy patients who have not responded to conventional antiemetics, and anorexia and weight loss in patients with AIDS. Nabilone is a Schedule II medication, with high potential for mental health side effects and addiction.
Sativex, a liquid extract from cannabis plant, is used as oral spray (“liquid marijuana”), contains THC, cannnabidiol (CBD), and other cannabinoids. Sativex has been approved for neuropathic pain, emesis, overactive bladder, and spasticity in several countries including England, Canada and Spain. Phase III studies of Sativex are currently underway in the US, thus it does not have a schedule assigned to it.
These medications have been approved for specific indications (nausea, vomiting, cachexia) and are currently studied for a number of new indications, such as spastic syndromes, neurological disorders, neuropathic pain, and other pain syndromes, among others. Note that use of medications that have been tested and approved by the FDA is not controversial. What is objectionable is that current efforts to legalize cannabis crude plant use state legislative processes to bypass federal regulatory processes that were put in place specifically to protect the public health.
Suggested but as of yet not FDA-approved indications for smoked cannabis and/or cannabinoids include spastic syndromes in neurological disorders, pain syndromes, and glaucoma. We reviewed about 70 studies of oral cannabinoids and the few available studies of smoked cannabis for a number of medical indications. As expected, prescription cannabinoids are effective antiemetics and appetite stimulants, and some studies report their effectiveness as adjunct therapy in chronic pain syndromes, spasticity, and glaucoma. Similar results are reported by the few studies of smoked cannabis plant for these same indications. As noted earlier, safe and effective alternative treatments for all these syndromes are available. Studies assessing psychological aspects of smoked cannabis and prescription cannabinoids uniformly report undesired effects: acute psychosis, poorer prognosis of chronic psychosis, or cognitive dulling in medical patients. In other words, in addition to a number of adverse medical effects (next section), psychological effects of cannabis are common and detrimental. Unfortunately, we found no long-term studies investigating whether and how frequently chronic use of small amounts of cannabis for medicinal purposes develops into cannabis abuse and/or addiction.
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