Most studies on the potential of marijuana, classic hallucinogens, 3,4-methylenedioxymethamphetamine, and ketamine have been small with methodological flaws, but the promising results from existing studies suggest that larger studies are warranted, said William M. Suavé, MD, medical director, Greenbrook TMS NeuroHealth Centers, during a presentation on the therapeutic potential of illicit drugs.
During a session at the 2017 Neuroscience Education Institute (NEI) Congress, William M. Suavé, MD, medical director, Greenbrook TMS NeuroHealth Centers, gave a presentation on the therapeutic potential of several illicit drugs.
The first drug Suavé focused on was marijuana. Substantial evidence from the National Academies of Sciences show that cannabis is beneficial for chronic pain, chemotherapy-induced nausea, and spasticity in multiple sclerosis (according to patient reports). However, the evidence also shows that cannabis is associated with the risk of respiratory symptoms, motor vehicle crashes, lower birth weight, and psychosis.
“There is evidence that some individuals are replacing the use of conventional pain medication with cannabis,” said Suavé. Cannabis was associated with a 65% reduction of opioid use in patients with chronic pain.
However, there are adverse effects associated with both short-term and long-term use of cannabis, said Suavé. Effects of short-term use include impaired short-term memory, motor coordination, and judgment; and paranoid ideation and psychotic symptoms in response to high doses of tetrahydrocannabinol. Effects of long-term or heavy use include altered brain development, symptoms of chronic bronchitis, increased risk of psychosis disorders, and cognitive impairment.
According to Suavé, medical marijuana is not a viable prescription option currently because drug approval standards require a consistent, pure, and well-defined chemical formulation; safety data in healthy populations and in specific medical disorders; a consistent, well-defined pharmacokinetic profile; efficacy data in specific medical disorders; and warnings regarding all potential side effects. Currently, for medical marijuana, compounds may vary from plant to plant, dosing is not well regulated, and there are residual impurities.
Suavé then discussed the use of psychedelics due to the renewed interest in the therapeutic value of hallucinogens. Typically 1 or 2 doses would be delivered in the context of psychotherapy to aid several disorders including depression, anxiety, addiction, and alcoholism. Classic hallucinogens include 2 classes of alkaloids: tryptamines and phenethylamines. Non-classic hallucinogens include 3,4-methylenedioxymethamphetamine (MDMA) and dissociative anesthetics.
The mechanism of action for classic hallucinogens is the exertion of effects primarily through the prefrontal cortical 5HT2A receptor agonism. Most studies report therapeutic effects that correlate with the level of “mystical” experience, said Suavé. There is a decreased brain connectivity in the default mode network, followed by the establishment of new connections.
“Hypothetically, this rewiring of the brain replaces disputed connections underlying psychiatric conditions with healthier connections,” said Suavé.
Small studies have shown the benefits of psilocybin on treatment-resistant depression; anxiety and depression associated with cancer; obsessive complusive disoder; and smoking cessation. A meta-analysis of randomized control trials concluded that a single dose of lysergic acid diethylamide, aka LSD, in the context of an alcoholism treatment program may decrease alcohol use.
Risks of these classic hallucinogens include dizziness, weakness, dilated pupils, tremors, and rare prolonged psychosis.
MDMA, also known as “ecstasy,” originated as a potential therapeutic agent. The FDA has recently approved phase 3 trials testing MDMA for patients with posttraumatic stress disorder (PTSD). MDMA has shown to increase motivation to engage in therapy due to its stimulating effect, reduce hypervigilance associated with PTSD, and allow reflection on traumatic memories during psychotherapy without being overwhelmed.
“Marijuana, classic hallucinogens, MDMA, and ketamine have all shown some evidence for therapeutic applications in a wide variety of psychiatric and neurological conditions; however, Schedule I status severely limits ability to research,” concluded Suavé. “Most studies to date are small, underpowered, and have other methodological flaws; however, promising results from existing studies suggest that larger studies are warranted.”