How CBD interacts with THC

    November 09, 2022 4 min read

    How CBD interacts with THC

    One of the apparent features of medications that combine cannabidiol (CBD) with delta-9 tetrahydrocannabinol (THC) is that the presence of CBD makes higher doses of THC possible to administer without increasing the usual risk of adverse side effects. CBD counteracts psychoactive and sedative effects of THC without interfering with beneficial effects, like muscle relaxation or attenuation of spasticity. How this works is not yet clear. Studies conflict, moreover, as to whether CBD increases or decreases other effects, behavioral and cognitive, of THC. Do the two compounds act independently of each other? Do they interact? Is exposure to one a function of systemic changes elicited by the other? The mechanisms of action of each are complex, and not completely understood yet, so these questions are not resolved. There is much that is known, however, from preclinical evidence and from a few preliminary human studies. We have written about some of the possible THC/CBD synchronies, antagonisms, and interactions elsewhere, focussing on particular therapeutic areas. It is worthwhile here to consolidate what is known generally, across therapeutic foci. 

    Preclinical evidence

    Two reliable effects of THC in preclinical animal models are lowering of body temperature and reduction of spontaneous physical motion. CBD has been reported both to potentiate these and attenuate them. What seems to matter is relative dosing, and possible timing of dosing, though conclusions about the exact relationship between these and their overall effects are inconsistent. CBD by itself has negligible effects on either locomotor activity or body temperature in mice and rats. Nor, interestingly, does it seem to modulate the hypothermic or hypolocomotor effects of cannabinol, another cannabinoid, in rats. 

    Another effect of THC is a decrease in sensitivity to discomfort. CBD has been shown to potentiate this, though only when ratios of CBD to THC are high – and even here, results are not completely consistent.  (It works well in anesthetized rats, but not in animals that are awake.) Tempting as it is, the conclusion that CBD synergizes in pain relief with THC is not completely safe to draw. 

    THC-induced anxiety and depression-like behavior is well described. Evidence for the effects of CBD on these is limited. CBD has potentiated the anxiogenic effects of THC in rats treated long-term at a 1:1 ratio. In another study, CBD was either anxiogenic or anxiolytic in rats depending on what behavior was being measured. In a third study, acute administration of CBD attenuated THC-induced social anxiety. Thus, CBD may have mixed effects on THC-induced affective changes. Or it may be that CBD acts on these variables by itself. We have written elsewhere on how CBD administered alone has reduced compulsive behavior in mice. 

    In complex cognitive tasks, CBD by itself has little or no effect. But it does seem, from numerous primate studies and one human study, to have an ability to counteract or even reverse detrimental cognitive effects of THC. Evidence is, in the slim body of study on memory recall, that the protective effect is due to pharmacological interactions, and not to differences in subject intelligence. This ameliorative effect on THC-induced reduction in higher cognitive tasks has not been reported in any rodent studies. 

    Human trials

    Human data on THC-CBD interaction derives from a small body of population-based studies and a smaller body of clinical trials. 

    In humans, THC reliably increases anxiety, in a dose-dependent manner. Studies combining CBD or examining CBD alone suggest that CBD functions as a general, and mild, anxiolytic, but appears to have more pronounced effects in lowering THC-induced anxiety. We have written on these particular studies in other posts. 

    Chronic and acute exposure to THC produce dose-related cognitive impairments in executive function, abstract ability, and decision making. The most pronounced effects are on verbal learning, short-term memory, working memory, and attention. CBD by itself does not appear to affect these. There is evidence that it decreases the impairing effects of THC, however. This has been observed in population studies and in laboratory experiments. The same general effect has been noted in at least one large crossover study in social cognition. 

    THC, of course, is psychoactive in the sense that it intoxicates. It can also elicit paranoia, conceptual disorganization, and perceptual alterations, that can be measured on validated rating scales. CBD, which does none of these things, may very well counteract them. This is being studied extensively in humans, as is CBD’s putative role in reducing symptoms of psychotic disorders. Evidence from population studies is that CBD has a protective influence on long-term effects of cannabis use. In laboratory studies, pretreatment with CBD associates with lower THC-induced psychotomimetic effects, including paranoia. In another early and influential trial, CBD reversed acute binocular impairment, a feature of some forms of schizophrenia, that was induced by the CB1 agonist, nabilone. Numerous studies now exist supporting the premise that CBD not only has the ability to reverse pseudo-psychotic effects of THC, but may function as an antipsychotic agent in its own right. 

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    The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.