By Matthew Warren

Over the past decade, neuroimaging studies have provided new insights into how psychoactive drugs alter the brain’s activity. Psilocybin – the active ingredient in magic mushrooms – has been found to reduce activity in brain regions involved in depression, for example, while MDMA seems to augment brain activity for positive memories.

Now a new study sheds some light into what’s going in the brain when people smoke cannabis – and it turns out that the effects can be quite different depending on the specific strain of the drug. The research, published recently in the Journal of Psychopharmacology, suggests that cannabis disrupts particular brain networks – but some strains can buffer against this disruption.

Cannabis contains two major active ingredients: tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for many of the drug’s psychoactive effects, such as the feeling of being stoned and the anxiety that people sometimes feel, as well as feelings of euphoria. High-THC strains of cannabis – known as skunk – are commonly consumed, with modern strains often having little CBD content, say the authors, and this has been suggested to put smokers at higher risk of developing psychosis. CBD, which is present at varying levels in other recreational strains of cannabis, doesn’t produce intoxication but may reduce anxiety and psychotic symptoms, suggesting it could block potentially harmful effects of THC.

However, few neuroimaging studies have examined how brain activity is influenced by different concentrations of these two ingredients. So Matthew Wall and colleagues decided to look at the neural effects of two strains of cannabis: one high in THC but with no CBD, and the other with high levels of both compounds.

The team recruited 17 participants who used cannabis fairly regularly but not heavily. All participants completed three sessions; in each session they were given one of the two strains of cannabis, or a placebo that didn’t contain either compound but still smelled like the drug. Half an hour after inhaling the vaporised drug, the participants had an MRI scan to measure their resting brain activity. After the scan they rated the intensity of the drug’s effects, scoring themselves on measures such as such as how anxious they were or how dry their mouth was.

The researchers then looked at patterns of connectivity within brain networks while participants were on the different drugs. They were particularly interested in the default mode network (DMN), which is active when we’re just resting and/or thinking about ourselves, and the salience network, which is involved in switching between this kind of internally-focused state and engaging with the outside world.

The team found that when participants smoked either strain of cannabis, the functional connectivity within their DMN was disrupted compared to when they smoked the placebo. But the pattern of disruption was strikingly different depending on the strain. Most prominently, the THC-only strain disrupted connectivity within an area of the DMN called the posterior cingulate cortex, and the amount of disruption in this area was directly related to participants’ ratings of the intensity of the drug’s effects. When participants took the strain that also contained CBD, disruption in this brain area disappeared, suggesting that CBD was blocking this effect. Differences between the two strains were also apparent in the salience network, where the THC-only strain similarly caused much more widespread disruption than the CBD strain.

These results suggest that CBD may act as a “buffer” against some of the neurological effects of THC, the researchers say, particularly those in the posterior cingulate cortex that are related to feelings of intoxication. This region also contains a high density of the receptors which THC acts upon, and other research has found that long-term use of cannabis can reduce the number of these receptors. This suggests that disruption in the posterior cingulate cortex could be related to the development of harmful long-term effects of the drug like psychosis and dependence – and that strains of cannabis that include CBD may be able to protect against these damaging effects.

The authors acknowledge that further evidence is needed for this theory – and it will also be important to study the effects of the strains in other populations. In this study, the researchers examined only semi-regular users who had never experienced any problems with drug-taking. The effects of cannabis in the brain could be very different in this group compared to those who have never taken the drug – or those who have had negative experiences with it.

Nevertheless, understanding that not all strains of cannabis are created equal is important in a time where the drug is becoming more widely accepted, the authors say. “As cannabis transitions to legal/decriminalized status in many jurisdictions, understanding the neural effects of different strains of cannabis (with different levels of THC and CBD) is now a priority for public health,” they write.

—Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity

Matthew Warren (@MattbWarren) is Staff Writer at BPS Research Digest