Cannabis is a narcotic drug that is increasingly being legalized throughout the Western world for medicinal and recreational purposes. At the same time, more potent pharmaceutical formulations are used in terms of ∆9-tetrahydrocannabinol (THC) concentrations. THC is known to cause severe adverse effects and may lead to long-term weakness when used consistently in high doses.
A new Neuropsychopharmacology study investigates whether these negative outcomes could be mitigated by increasing the concentrations of cannabidiol (CBD) in these products.
Stady: Does cannabidiol make cannabis safer? A randomized, double-blind, cross-over trial of cannabis with four different ratios of CBD:THC. Image credit: IRA_EVVA/Shutterstock.com
Low-frequency cannabis users have been reported to experience severe loss of memory and attention with high-THC cannabis preparations, along with psychotic symptoms. Over long periods of use, this may lead to an increased likelihood of developing psychosis and developing a cannabis use disorder.
As a chemical, CBD fails to affect cognitive function and prevent the development of psychosis, with the risk of both being reduced among high-CBD cannabis users, regardless of their frequency of use. When CBD is given for the first time, followed by THC, it has been reported to attenuate the memory and psychotic effects of THC in light users, but not with frequent use.
about the study
The current study examines the acute effects of cannabinoids at four different doses of CBD in relation to THC. CBD:THC ratios of 0:1, 1:1, 2:1, and 3:1 were tested in 46 healthy volunteers between the ages of 21 and 50 who used cannabis infrequently. More specifically, the participants had used the drug one or more times in the past but no more than once per week for the past year.
None of the study participants had a substance use disorder or used industrial cannabis.
The current study followed a randomized, double-blind pattern using vaporized cannabis containing 10 mg THC and either 0, 10, 20, or 30 mg CBD. The researchers assessed their effects on cognition in relation to verbal recall using the Hopkins Verbal Learning Task. At the same time, psychotic symptoms were assessed using the Positive and Negative Subscale (PANSS).
Study participants first inhaled cannabis, after which they completed a set of cognitive tasks and pleasurable effects were assessed based on their enjoyment of chocolate and music compared to baseline. Then the participants were asked to buy something in a store in the hospital.
Then, the study participants were given time for the effects of the drug to wear off. Finally, they completed questionnaires describing their psychological experiences, including persecutory thoughts, a self-assessment of psychotic thoughts, and a visual analog scale of their subjective feelings after drug use.
Finally, they completed an interview for the PANSS-P application.
What did the study show?
In all cases, the levels of the THC metabolite and THC in the blood were similar. However, peak CBD levels went up with the THC:CBD ratio.
THC exerts the same effects on all ratios, with twice as much immediate and delayed verbal recall compared to baseline, regardless of the presence or proportion of CBD. Here, THC causes higher rates of psychosis-like intrusive thoughts, both immediate and delayed.
Positive psychotic effects were significantly greater after inhalation, with half of all participants showing an increase in their PANSS-P scores by three points compared to baseline in all proportions and without significant differences between proportions. Psychotic thoughts also increased across the group without any difference between the different proportions.
However, persecutory thoughts did not increase with drug use in any proportion.
Other tests have shown that the pleasurable or euphoric effects are evenly distributed, regardless of the CBD:THC ratio. In addition, feelings of euphoria did not correlate with plasma levels of either compound.
While heart rate increased after inhalation, there were no changes in blood pressure or temperature. However, coughing during inhalation was significantly greater with the CBD dose. Furthermore, with the longer periods required to inhale the full dose, peak concentrations were reduced at higher rates of CBD:THC.
What are the effects?
Co-administration of CBD with THC had no effect on the induction of cognitive impairments or psychotic symptoms after cannabis use.. “
Moreover, the presence of CBD in increasing proportions did not alter the subjective feeling of high or the pleasurable effects of THC.
The current study is important, as it measured these effects with CBD:THC ratios that are commonly found in recreational or medicinal cannabis. Unfortunately, many of the participants dropped out at the first visit, more so at a 3:1 ratio, due to the unpleasant effects of the medication.
The remaining study participants may be less sensitive to cannabinoids, especially CBD, but they still reported significant changes on cognitive and psychological tests.
The preliminary observation that CBD does not modify the psychoactive or cognitive effects of THC confirms previous studies; However, two previous studies reported weakening of these effects with CBD. These used larger doses of CBD that are often greater than those typically found in medical or recreational cannabis. These doses may require routes of administration other than inhalation.
Conversely, one previous study reported lower risk with higher CBD:THC ratios which may be explained by the fact that plants that produce cannabis in higher ratios do so by producing more CBD at the expense of THC, as both come from the same precursor compound. .
Thus, the alleged reduced risk from using high CBD varieties may not be an effect of the high CBD content, but rather the relatively low THC content.. “
Study results show that CBD offers no protection against the acute effects of THC; However, the potential long-term protection remains to be studied. Meanwhile, it appears that CBD content is not a determining factor in regulating or determining cannabinoid combinations and may not mitigate the harmful effects of THC.
- Englund, A.; , Oliver, d. Chesney, E.; et al. (2022). Does cannabidiol make cannabis safer? A randomized, double-blind, cross-over trial of cannabis with four different ratios of CBD:THC. Neuropsychopharmacology. doi: 10.1038/s41386-022-01478-z.