UK newspapers this week reported on a study which had two findings of particular interest to people using or hoping to access medical cannabis.
Firstly, it concluded that just a single dose of THC – the psychoactive compound found in the cannabis plant – can induce psychotic and other psychiatric symptoms in healthy adults with no history of a major mental illness.
Secondly, it stated that it “found no consistent evidence” that cannabidiol (CBD) moderates the effects of THC “in healthy volunteers”.
This may have been particularly alarming to parents of children with epilepsy who are taking medical cannabis containing low level THC.
CBD is believed to play an important role in counteracting any side-effects of the THC, thus preventing children experiencing a high, for example.
The study, funded by the Medical Research Council and initially published in the Lancet, and various newspapers, assessed the results of 15 previous studies involving 331 people.
Here Professor Mike Barnes, a consultant neurologist and chair of the Medical Cannabis Clinicians Society, gives his views on the findings:
“The report states that if a person takes THC in a single dose, its effect is not modulated by CBD given at the same time. So let’s look at the science behind that.
“CBD is a negative allosteric modulator of the CB1 receptor in the brain and elsewhere. That means CBD binds to the receptors that THC binds to, albeit in a slightly different place. So THC can’t lock onto receptors with CBD already bound to them
“The CBD doesn’t do anything to the receptor, it just changes it so the THC can’t lock onto it. Therefore if you give CBD, there is less effect of the THC because there are less receptors for it to bind to. That is a scientific fact. It’s not arguable, it’s not speculation, it’s factual.
“So therefore if you give CBD, we know there will be less THC effect. That is borne out in both human and animal studies. We know for certain that if people are on THC, there’s less THC side effects if they are on CBD at the same time.
“That’s known in the cases of children with severe epilepsy, for example, and that’s why the fundamental principle of cannabis medicine is that you start with a CBD product, build up that dose and then if necessary, you add in THC.
“If you are already on a background of CBD, you don’t get so much of the THC side-effects that you might not want, like the recreational high or the psychotic problems referred to in the report.
“Moving onto the issue of inducing psychosis from one dose of THC. We know that THC can cause psychosis but only rarely and only if you’ve had it before or if you have a first degree relative with it.
“So, if you’ve got a history of schizophrenia or psychosis, you shouldn’t really prescribe THC. It’s not an absolute contraindication, it’s a relative contraindication.
“For example, if you has a schizophrenic episode in your teens but you’re now 50 and you’ve got chronic pain, I would still prescribe THC. But if you were in your 20s and actively schizophrenic, with psychotic reactions, I wouldn’t prescribe THC. We’ve known that THC and psychosis go together for years, so that’s not new.
“In the study, they’ve assessed the administering of one dose of THC with CBD and concluded that it didn’t modulate the effect. But they also say in their own paper that the limitations of that study “contrast with the results of several other studies and may reflect limited power over the analysis”. So they accept the report is flawed.
“The findings on non-modulation go against all the known facts of THC and CBD – scientifically, and in terms of animal models and human experience.
“But also, a single dose doesn’t reflect normal usage which usually involves taking multiple doses daily.”
More info on the study
Researchers identified 15 studies that studied participants’ psychiatric symptoms following the acute administration of intravenous, oral, or nasal THC, CBD, and placebo in healthy participants.
The studies included scores for an increase in severity of positive psychotic symptoms (including delusions and hallucinations), negative psychotic symptoms (such as blunted affect and amotivation), and general symptoms (including depression and anxiety), which were compared after THC administration versus placebo.
A change in symptoms with an effect size of 0.4 or more was considered clinically important, and an effect size of more than 0.70 was considered a large effect.
The doses of THC in the meta-analysis ranged from 1.25mg to 10mg, leading to peak THC blood levels of 4.56 to 5.1 ng/ml when orally administered and 110-397 ng/ml when injected or inhaled.
These blood levels are comparable to those seen shortly after smoking a single typical cannabis joint containing 16-34mg of THC.
Compared to placebo, THC was found to induce significantly more severe positive psychotic symptoms (average effect size of 0.91), negative symptoms (average effect size 0.78), general symptoms (average effect size 1.01) and total symptoms (average effect size 1.10). The effect sizes remained significant for all types of symptom regardless of sex, age, dose, route of administration, prior cannabis use and tobacco use.
However, intravenous administration had more pronounced effects than inhaled THC on psychotic and negative symptoms, while there were insufficient studies to assess the effect of oral THC. Greater induction of psychotic symptoms by THC was associated with lower rates of tobacco use, and greater induction of negative symptoms was associated with a higher age.
The authors also reviewed four studies that examined the effects of CBD on the development of the same psychiatric symptoms, compared to placebo, and no significant differences were found. In studies that focused on whether CBD counters THC-induced symptoms, one study identified reduced symptoms, using a modest sample, but three larger studies failed to replicate this finding.
The authors highlight several limitations to their study. Their finding that psychotic symptoms were not moderated by dose or by prior cannabis use contrasts with results from several studies and may reflect limited power in the analysis.
They suggest that further work is needed to clarify the effects, particularly at the level of individual symptoms. The authors identified potential publication bias, where significant findings are more likely to be published than lower effect sizes.
However, they found that the better the quality of the study, the greater the effect size, suggesting that their results – which also included lower quality studies – may in fact underestimate the size of the effect of THC on inducing symptoms.
This study was funded by the Medical Research Council. It was conducted by researchers from Kings College London, South London and the Maudsley NHS Foundation Trust, Imperial College London, Leiden University Medical Hospital, Yale University School of Medicine, Connecticut Mental Health Center and VA Connecticut Healthcare System.
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