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One reason some physicians look askance at the vernacular cannabis movement is that it can, in its sometimes quasi-religious devotion to the plant, seem almost cultlike. Kristen Park, an epileptologist at Children’s Hospital in Colorado, told me that after Gupta’s CNN story aired, patients from around the country seeking medical cannabis inundated the hospital. She had no data at that point on its efficacy and did not recommend it. The Epidiolex trials have provided some evidence of effectiveness, Park told me, but she still frets over the phenomenon. Sometimes parents of patients refuse established epilepsy treatments in favor of cannabis products, she says, because these are perceived as somehow natural and thus superior to standard medicines. Other parents insist cannabis is helping their children when, in her view, it clearly isn’t — and they refuse to stop using it when they should move on to other treatments. “Because of all the hype, people somehow think this is a cure-all and a treatment that will fix everything,” she told me. What’s lost on many, she says, is that even if CBD helps, it’s still just another drug, and no drug works for everyone all the time.
In June 2018, just five years after that meeting — an instant in drug-development time — the F.D.A. approved GW Pharmaceutical’s CBD extract as a treatment for two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. And three months later the D.E.A. rescheduled this first CBD drug (but not THC) to Schedule 5, meaning it was now considered to have low potential for abuse.
A follow-up study will prophylactically treat a large group of these patients thought to be teetering on the edge of psychosis. Current schizophrenia treatments merely attempt to manage the disorder once it has already emerged. A medicine that slows or prevents the disease from taking root altogether, almost like a vaccine, would address a huge unmet need. “If it works, it will be a revolution,” José Crippa, a neuroscientist at the University of São Paulo who is involved in the project, told me.
It’s reasonable to ask why the CBD naturally present in cannabis doesn’t protect recreational users from the negative effects of THC. In older varieties, where the CBD-to-THC ratio was closer to 1-to-1, maybe it did. But today’s strains typically contain about three times as much THC as the cannabis smoked recreationally even as recently as the 1990s, while CBD concentrations have fallen by about half in the same period, according to a recent University of Mississippi study on black-market marijuana. And precisely because the proportions between the two cannabinoids have become so skewed — the ratio of THC to CBD has risen to 80 to 1 from 14 to 1 in two decades — lots of modern cannabis is potentially much more toxic for the brain, says Hurd, who is the director of the Addiction Institute at Mount Sinai.
The D.E.A.’s classification of cannabis as a Schedule 1 drug, alongside heroin, peyote, ecstasy and LSD, has made it difficult for American scientists to study. Much of the research into its therapeutic potential comes from other countries, including Brazil. In the 1970s, Antonio Zuardi, a neuroscientist at the University of São Paulo, began looking into how cannabinoids affect mental states. Large quantities of THC could cause anxiety and paranoia in volunteers, he discovered, but CBD could attenuate the anxiety-provoking and psychoticlike effects of THC. Later studies by Zuardi and his colleagues showed that a large dose of CBD, when given to volunteers who feared public speaking — that is, who suffer from social anxiety — blunted the flight-or-fight response, measured by increases in heart rate, blood pressure and skin conductivity, prompted by having to address others. These were small studies, and the amount of CBD involved, which was 600 milligrams in the social-phobia study, is greater than what users might consume these days in some CBD gummies, for example, but relieving anxiety is nonetheless one of the most widely reported reasons people use CBD.
The epilepsy drugs that had been approved to date, none of which had helped Ben much, typically targeted the same few ion channels and receptors on the surface of neurons. But CBD worked on different and still somewhat mysterious pathways. If she could find a suitable CBD extract, Jacobson thought, she might have a truly new class of drug for Ben. The other experimental drugs and devices she had heard about at epilepsy conferences were under development, unapproved by the F.D.A. and thus largely unavailable. But medical marijuana had been legal in California since 1996, so CBD was theoretically accessible right away.
CBD may also have antipsychotic properties. In susceptible individuals, its sister cannabinoid THC can, in high doses, induce psychotic symptoms, and heavy marijuana use early in life has been linked to an increased risk of developing psychotic disorders, possibly because it alters brain development. But just as Zuardi discovered that CBD can blunt anxiety, scientists at King’s College London have found evidence that CBD can lessen the psychosis-producing effects of THC and maybe help treat schizophrenia, a disorder whose main symptom is psychosis. The scientists are now testing CBD as a prophylactic to prevent schizophrenia from even emerging.
Cannabis has been used medicinally for thousands of years in Asia, where it was probably first domesticated before traveling to, among other places, Africa. It was almost certainly introduced multiple times to the Americas, first from Africa to South America through the slave trade — in Brazil it’s still known by an African name, diamba — but also to the Caribbean. Indian indentured laborers probably brought it to Jamaica, where it’s called by an ancient Indian name, ganja.
UPDATE: On November 25, 2019, the Food and Drug Administration (FDA) published a revised consumer update regarding safety concerns about cannabidiol (CBD) products. Due to limited research data, the FDA is unable to declare CBD products safe, according to the updated statement. The FDA warns that CBD can cause liver damage, increased drowsiness, and a number of other side effects. The impact of daily CBD use over a sustained period of time is unknown. Likewise, the FDA says there is insufficient research on the effect of CBD on the developing brain, on fetuses, and on the male reproductive system. The FDA has approved only one CBD product, which treats two rare forms of epilepsy. In late November, it issued warning letters to 15 companies for illegally selling products containing CBD.
What Is CBD? Does It Help ADHD?
Anecdotally, this outcome appears common for half of those trying CBD on their own — regardless of the quantity, quality, or type used. The other half claim some positives with regard to CBD and ADHD: “I was able to relax” or “I felt less manic” are common refrains. The problem, as Dr. Mitchell and the broader community of ADHD and CBD researchers point out, is a dearth of studies around CBD. No single research team has yet studied the possible effects — good or bad — of CBD oil for ADHD symptoms specifically.
Is CBD Legal? Is It Safe?
And while CBD may potentially benefit some patients with ADHD, “One is doing an experiment on oneself by taking CBD for ADHD,” Evans adds. “CBD is anti-inflammatory and I’m not sure there is good evidence mechanistically that for ADHD it might be helpful.”