This is a recurring column on clinical research in the early stages of development, what is referred to as phase 1. These are treatments that are being used for the first time in a small number of human patients to determine safety, dosing and general pharmacological activity.
The hypes and hopes of medical cannabis
The hype is real in medical cannabis: Left and right, retailers tout the healing potential of cannabidiol oils in just about any condition — but research, though budding, remains thin.
Regulatory issues have long stymied research efforts to dig into the substance and actually prove what therapeutic effects cannabis can have, and now that legal infrastructure is slowly but surely allowing medical cannabis use, scientists and regulators alike are scrambling to catch up to the market demand.
"It's a matter of following … established rigorous trial methods," Michael Bloomfield, senior clinical research associate at University College London's psychiatry division, told S&P Global Market Intelligence in an interview. "It's really understandable that that hasn't been the case because there have been lots of regulatory difficulties in studying medical cannabis."
Only two cannabis-based medicines are regulatory body-approved worldwide, both made by U.K.-based GW Pharmaceuticals PLC.
Because of strict regulations, the lack of research — particularly randomized controlled trials — in medical cannabis has led to a lack of standardization in manufacturing, dosing and prescribing the substance.
Furthermore, obtaining cannabis for research purposes can be tricky in the U.S., where cannabis remains a Schedule I drug. The U.S. Drug Enforcement Agency must review applications from manufacturers hoping to produce marijuana for federally approved research projects.
The DEA said Aug. 26 that it has more than doubled the production quota for marijuana each year over the past two years because of increased projections for such research.
Safety is also at the forefront of research concerns, especially with the cannabinoid THC, known for its psychoactive properties.
"We know that in some people, [cannabis with THC] can cause addiction, dependence," Bloomfield said. "There's also particular concern in young people and about increasing the risk of psychosis … we just need to be a bit cautious when we're talking about the use of these treatments in children and adolescents."
Still, cannabis has been earmarked as a potentially promising therapy for treating pain, especially to replace the use of opioids, as well as psychiatric and other neurological disorders, which have limited treatment options.
An alternative to opioids
The Cannabis for Opioid Substitution Trial evaluated the potential of medical cannabis to replace opioids to treat pain. According to principal investigator Ira Price, the recently completed study enrolled 1,200 patients in Canada who were taking prescription opioids to treat chronic cancer and non-cancer pain syndromes.
Among those patients in the observational phase 1 trial, opioid use was reduced by over 80%, with over 50% of those patients coming off of their opioids altogether, according to Price, an assistant professor in the division of emergency medicine at McMaster University.
Patients used any form of medical cannabis obtained from a licensed producer in the trial.
The trial, commissioned by Canadian cannabis producer Northern Green Canada and conducted by contract research organization Cannabis Research Associates, also included data on which strains of medical cannabis most patients used to help decrease their opioid use.
"We picked the top bunch of strains, and [Northern Green Canada] would then … formulate a specific extraction," Price said.
The next step in the trial, results of which have been submitted to a medical journal for publication, is to conduct a randomized controlled trial using that specific medical cannabis formulation, Price said.
Price said the program is intended for a regulatory pathway.
"It should definitely be one of the major priorities specifically because we're sitting at one of the worst times in history for opioid abuse," Price said.
Trial of cannabis for essential tremor
Meanwhile, a combination of CBD and THC is being tested for essential tremor, a neurological movement disorder with no approved therapeutics. Essential tremor, which causes involuntary and rhythmic shaking, affects approximately 1% of the population and up to 5% of those over 65, according to the University of California, San Diego study.
The phase 1/2 trial will randomize 16 participants across two treatment groups, one with an oral capsule of CBD/THC, and another with a placebo capsule.
One of the trial's main goals is to better understand dosing, tolerability and safety of the substance.
According to principal investigator Fatta Nahab, anecdotal evidence from patients had suggested cannabis can have a positive impact on essential tremor.
Canada-based Tilray Inc. is supplying the CBD/THC formulation and placebo capsule for the trial, along with some other support, said Nahab, an associate professor of neurosciences at UCSD.
Should the drug demonstrate safety and efficacy, larger, multi-site trials will likely come next. Completion of the trial is expected within one year, Nahab said.
THC in bipolar disorder
Researchers at Yale University are looking into THC's effects on adults with bipolar disorder, specifically change in verbal memory, function and other elements like mood and anxiety.
The 40-participant phase 1 trial randomized healthy volunteers and bipolar disorder patients across three groups: one taking 4 milligrams of inhaled THC via a vaporizer, another taking 2 milligrams and the third group taking an inhaled placebo containing no active cannabinoids.
Bipolar disorder is characterized by episodes of both mania and depression.
The study was completed in July 2019, according to Clinicaltrials.gov.
Principal investigator Mohini Ranganathan, associate professor of psychiatry at Yale, has previously studied CBD in schizophrenia, comparing the substance against antipsychotic drug amisulpride. That trial, which concluded in May 2018, found that both drugs achieved clinical improvement in patients, but CBD displayed a "significantly superior" safety profile.