Over the past decade, marijuana has had quite a run. Seventeen US states and the District of Columbia now allow recreational use of marijuana; only 13 states have not yet legalized it for either medical or recreational purposes. But what do we really know about the relative benefits and risks of the popular and remarkably complex cannabis plant? Get the best results by visiting and shop the darts.
Researchers have long asserted that the science has badly trailed the claims and counterclaims of supporters and detractors. Over the past 5 years, however, high-quality trials and reviews have begun to close the gap. Of the cannabis plant’s roughly 140 unique chemical constituents, or phytocannabinoids, 2 of the best studied are Δ-9-tetrahydrocannabinol (THC), the plant’s main psychoactive ingredient, and cannabidiol (CBD).
In an April 2021 telebriefing on cannabis and health sponsored by the nonprofit journalism service SciLine, experts noted that CBD is gaining prominence mainly because of its significant differences with THC. “What is unique about CBD is that although it is psychoactive—so we think that it is helpful for some indications for the central nervous system and in the brain, like anxiety, and perhaps pain—it is not intoxicating,” says Ziva Cooper, PhD, director of the University of California, Los Angeles Cannabis Research Initiative. Some scientists believe that other phytocannabinoids and hundreds of separate chemicals called terpenes might likewise have therapeutic effects, although Dr. Cooper cautions that most research on these chemicals has so far been limited to animal studies.
Conclusive or Substantial Evidence for Some Effects
Despite the unknown effects, evidence is steadily mounting that at least some cannabis health claims are backed by science. In 2017, the National Academies of Sciences, Engineering, and Medicine released The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, a report by an expert committee that reviewed the available evidence for 20 indications.1 As expected, the committee found conclusive evidence that oral cannabinoids were effective in preventing and treating chemotherapy-induced nausea and vomiting. The committee also found substantial evidence that cannabis or cannabinoid compounds were likely to significantly reduce the symptoms of patients with chronic pain and that the short-term use of some oral cannabinoid medications improved the self-reported symptoms of adults with multiple sclerosis–related muscle spasms.
The committee found moderate evidence that cannabis or cannabinoids could improve the symptoms of fibromyalgia and, at least in the short term, improve sleep disturbances associated with obstructive sleep apnea syndrome. The report cited limited evidence of effectiveness for increasing appetite and decreasing weight loss associated with HIV and AIDS, for improving the symptoms of Tourette syndrome and posttraumatic stress disorder, and for aiding the public speaking ability of patients with social anxiety disorders. Dr. Cooper, a member of the review committee, emphasizes that most of the assessed studies did not use the cannabis plant itself, and none used medical dispensary products. “So, we have very little knowledge about the whole cannabis plant and what people are using,” she says.
Since the report’s release, other studies have offered compelling evidence that a purified extract of CBD called Epidiolex is effective in alleviating epileptic seizures associated with 2 rare but severe conditions: Lennox-Gastaut syndrome and Dravet syndrome.2 On the basis of that evidence, in fact, the Food and Drug Administration (FDA) approved Epidiolex in 2018, and this made it “the first FDA-approved drug that contains a purified drug substance derived from marijuana” according to the agency.
Igor Grant, MD, director of the Center for Medicinal Cannabis Research at the University of California, San Diego, says that the National Academies report agreed with his group’s longstanding conclusions about the usefulness of cannabis for managing pain, particularly neuropathic pain. “I think what is not known is how enduring the therapeutic effect is,” he says. At least so far, Dr. Grant says, studies have suggested that low-dose cannabis is a relatively safe pain treatment and provides relief comparable to the relief provided by some commonly used drugs such as the anticonvulsant lamotrigine, although not as much relief as some antidepressants.
The effectiveness of cannabis against low- to mid-grade chronic pain has, in fact, widened discussions about its potential as a safer alternative to prescription opioids. A 2014 analysis found that US state laws permitting medical cannabis “are associated with significantly lower state-level opioid overdose mortality rates.”3 In a 2019 commentary, Thomas Clark, PhD, a professor of biology at Indiana University South Bend, cited evidence that moderate use of marijuana can help to reduce reliance on prescriptions for multiple drug classes. The result of fewer overdose deaths from more dangerous drugs, he argued, should be factored into the potential health benefits of cannabis.4
A Drug of Many Contradictions
What is becoming clear, Dr. Grant says, is that cannabis seems to have a biphasic effect for many indications. It is ineffective at low doses, effective at modest doses, and then again ineffective, even harmful, at high doses. This effect can be readily observed with anxiety: Although cannabis has calming and antianxiety effects when taken in low to moderate doses, it can produce significant anxiety and even paranoia and hallucinations at higher doses.
One intriguing Center for Medicinal Cannabis Research study now underway is following up on initial but limited evidence suggesting that CBD may have some antipsychotic effects. “So, in other words, it may be a useful treatment for some forms of psychosis or schizophrenia,” Dr. Grant says. “If this turns out to be true, it would be really great because CBD has rather minimal side effects, whereas the drugs we use to treat schizophrenia have a lot of side effects.”
