Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey

This survey study (n=321) explored the subjective effects of psychedelics when used alongside cannabis. It was found that the use of cannabis alongside classic serotonergic psychedelics such as LSD and psilocybin led to a more intense psychedelic experience across a number of measures including; the Mystical Experience Questionnaire (MEQ) and the Ego Dissolution Inventory (EDI).

Abstract

“Rationale: Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce.

Objectives: The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis.

Methods: Participants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual ‘setting’ variables.

Results: The simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI.

Conclusions: Results imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.”

Authors: Joanna Kuc, Hannes Kettner, Fernando Rosas, David Erritzoe, Eline Haijen, Mendel Kaelen, David J. Nutt & Robin L. Carhart-Harris

Notes

A large amount of research is taking place regarding the use of psychedelics as prospective treatments for a range of mental health disorders. The number of clinical trials involving psychedelic’s continues to increase as these compounds have demonstrated both safety and efficacy when used therapeutically.

However, little is known about how psychedelic’s interact with other psychoactive substances. Understanding how drugs interact with one another is an important part of the drug development process as drug-drug interactions can influence the therapeutic outcome and can also lead to unwanted side effects.

Outside of the medical context, psychedelics are often used in tandem with other psychoactive substances. In the present study, researchers explored the subjective effects of psychedelics when used alongside cannabis.

This survey study (n=321) involved participants completing a set of questionnaires including; Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). The online surveys were completed seven days before and one day after a planned experience with a serotonergic psychedelic.

Main findings:

• The most commonly used psychedelic by the respondents was LSD (50.2%) followed by psilocybin (29.3%).
• 39% of survey respondents used cannabis alongside psychedelics while one-third of respondents admitted to using cannabis alongside LSD or psilocybin, either often or always.
• Cannabis use was associated with more intense mystical-type, ego dissolution and visual experiences, and more challenging experiences were associated with higher doses of cannabis.
• Although the study did not explore the molecular basis of the cannabis-psychedelic interaction, the findings suggest that there is a potential degree of overlap in the receptor targets of psychedelics and cannabis i.e the 5-HT2A receptor.

The authors of the study acknowledge that several limitations exist and thus, cannot definitively state that cannabis had a direct effect on respondents psychedelic experiences. For instance, the doses of the psychedelic or cannabis were not assessed and the time of cannabis consumption was not recorded.

Nonetheless, this study is the first to provide an insight into the effects cannabis has on the psychedelic experience. While the findings are important in terms of harm reduction for recreational drug users, they may eventually be extended to the therapeutic effects of these substances with further research.

Summary

4-Ho-MET, 5-HT, 5-HT1AR, 5-HT2AR, 5-MeO-DMT, AL-LAD, 6-Allyl-6-nor-LSD, ASC-Vis, CB1 Cannabinoid receptor type 1, CEQ, EDI, MANCOVA, MEQ, PTSD, THC, VAS, BIC, and VAS-Vis are used in research.

Introduction

Psychedelics are now being extensively researched as an addition to psychotherapy for treating various mental health disorders. Evidence suggests that the acutely experienced psychedelic state is critical for their efficacy.

Serotonergic psychedelics produce profound distortions in perceptual processes, mood and cognition, and are often associated with alterations in visual and other sensory perception, as well as synaesthesia. They also induce emotional effects, and cognitive effects, such as changes to the normal flow of cognition.

Use of psychedelics with other substances

Psychedelics are commonly used concomitantly with other psychoactive substances, such as cannabis, ayahuasca, and MDMA, to maximise positive effects and minimise negative effects. However, few studies have assessed the subjective experience of concomitant drug use quantitatively.

The two key chemical constituents of cannabis are THC and CBD, which act through cannabinoid type 1 (CB1) and type 2 (CB2) receptors, as well as serotonin (5-HT) receptors. This could lead to a synergistic interaction between serotonergic psychedelics and cannabis.

The current investigation might provide insights into the interactions between psychedelics and cannabis, which might have important consequences for psychedelic-assisted clinical theory. It might also provide data on previously unreported potential side effects of this polydrug combination.

Design

A software platform was used to recruit adults with the intention of taking a serotonergic psychedelic drug. They were asked to fill out several surveys at specified time points and the data from 321 participants was used in the current study.

The initial design includes 5 time points, but the current study included just two. The baseline time point took place 7 days before the planned experience, and the post-experience time point took place one day after the subject’s psychedelic experience.

Drug usage

Participants were asked to specify the psychedelic they used and to indicate the dose they used. The dose was then recoded into numerical Likert-scale 1 – 5 values, where 1 was equal to a low dose and 5 an extremely high dose.

Participants were asked if they used other types of drugs during their psychedelic experience, and to indicate the dose of each drug. The data were then recoded into numerical Likert-scale 0 – 3 values.

Setting, framework and environmental factors

Participants were asked questions about the setting and guiding framework of the retreat. This data was analysed as potential confounders.

Mystical Experience Questionnaire

The Mystical Experience Questionnaire (MEQ) is a 30 item scale that was developed by Pahnke and Richards and used in clinical and non-clinical work.

Visual subscales of the Altered States of Consciousness Questionnaire

The ASC includes 9 questions about elementary imagery, complex imagery and audio-visual synaesthesia. The total score is calculated as the sum of all 9 items.

Challenging Experience Questionnaire

The Challenging Experience Questionnaire (CEQ) consists of 26 questions and is used to assess the amount of challenge experienced by participants.

Ego Dissolution Inventory

The Ego Dissolution Inventory (EDI) is an 8 question questionnaire that was previously used in non-clinical work.

Emotional Breakthrough Inventory

The Emotional Breakthrough Inventory (EBI) consists of 6 items and a total score is calculated as the average of the 6 items.

Statistical analysis

Responses were recoded as numerical values, and subscale and total scores were computed for each questionnaire. Listwise deletion was performed for missing data.

Multivariate analysis of covariance

The samples were grouped based on subjectively described cannabis dose, and potential confounding factors were identified based on exploratory distribution of variables. The non-normal distribution of variables was not considered to be problematic for the quality of final output in regular linear models.

Pearson correlation coefficients were calculated to identify multicollinearity among the chosen confounders. The variance inflation factor (VIF) cut-off point was set to 5, indicating that multicollinearity was not a concern.

A MANCOVA analysis was performed using MEQ, ASC-Vis, CEQ, EDI and EBI scores as dependent variables, and the dose of cannabis as a fixed factor. Pillai’s trace was used as a test statistic, and post hoc Bonferroni’s correction was used to control multiple comparisons.

Regression modelling

To further investigate the psychological effects of cannabis dose, linear, quadratic and cubic regression models were computed and compared using the Bayesian Information Criterion. Only the model with the lowest BIC is reported.

Demographics

The survey involved 654 participants, of which 321 completed all time points. Males represented 68.8% of the sample.

Drug choices

39.3% reported using cannabis during the psychedelic experience, with 16.5% using low doses, 14.0% medium and 8.7% high. Psilocybin and LSD were most often used across all groups.

Across the whole sample, 10.6% used alcohol, 1.9% used stimulants and 25% used tobacco. Among those who used low doses of cannabis, 84.9% used no alcohol, 11.3% used a low dose of alcohol, 3.8% used a medium dose of alcohol and none used a high dose of alcohol. In the medium cannabis dose group, 86.7% used no alcohol, 8.9% used a low dose of alcohol, 2.2% used a medium dose of stimulants and 2.2% used a high dose of stimulants. In the high cannabis dose group, 71.4% used no alcohol, 21.4% used a low dose of alcohol, 3.6% used a medium dose of alcohol and 3.6% used a high dose of alcohol.

Identification of potential confounding variables

One-way ANOVA tests were used to identify variables that were significantly correlated with cannabis dose. These variables were included in further analyses, except for the psychedelic, which was distributed equally across all cannabis conditions.

A correlation matrix among the selected covariates was constructed to test for multicollinearity. The retreat setting factor was found to be highly correlated with the shamanic framework and live singing factors, and was thus excluded from the final model.

The effect of cannabis on the subjective psychedelic experience

Pillai’s trace value for cannabis was 0.097 (p = 0.009), confirming its relevance in the final model. Cannabis use interacted with psychedelic-use in terms of its effects on subjective experience.

Regression modelling results show that the presence of cannabis significantly altered the quality of a psychedelic experience in several dimensions.

The MEQ, ASC-Vis and EDI showed a positive linear relationship with increasing doses of cannabis, whereas the CEQ followed a quadratic trend. The EBI showed no relationship with increasing doses of cannabis, but the top range of obtained scores was lower with increasing doses.

Role of cannabis in modulating challenging experiences

The dose-dependent effect of cannabis on the various dimensions of CEQ during a psychedelic experience is illustrated by Fig. 5, where the overall CEQ score follows a quadratic trend, but univariate analyses of the subscales show that the effect is significant only in certain subscales.

Discussion

The current study investigated the effects of concomitant cannabis use on the subjective quality of a psychedelic experience. It found that cannabis use was associated with more intense mystical-type, ego dissolution and visual experiences, and less intense challenging experiences.

Cannabis induces subjective effects that are similar to some effects of psychedelics, such as euphoria, changes in perception of time, intensification of sensory perception and hyper-associative thinking. Furthermore, THC levels correlate positively with higher scores on the 5-Dimensional Altered States of Consciousness Rating Scale.

The study participants were not of any specific religious practices or indigenous groups, which might limit the implications of the study to practices outside of the mentioned contexts.

The synergistic effects between cannabis and psychedelics may be due to the overlap in receptor targets, as both drugs affect serotonergic systems and both drugs affect the 5-HT1A receptor, which is involved in the regulation of brain excitability.

The action of cannabis: anxiolytic and anxiogenic

Cannabis may exert differential, including potentially opposing effects, depending on dose and potency. The ratio of THC to CBD in cannabis products predicts whether cannabis is more likely to induce anxiogenic- or -lytic effects, with anxiolytic qualities largely induced by CBD, the nonintoxicating constituent of cannabis.

Psychedelics use in combination with cannabis was associated with reduced perceived grief, increased fear, and an association with the insanity subscale of the CEQ. This suggests that cannabis may limit the experiential acceptance, considered one of the key mechanisms of action in psychedelic-assisted psychotherapy for depression.

Limitations

We did not directly assess the dose of psychedelic or cannabis used, relying instead on the subjective report describing the perceived quantity. This report might be biased by various factors, including sample inaccuracy, poor inter-subject reliability and standardisation in assessment, previous drug experience and environmental/social factors.

The relationship between subjectively rated cannabis dose and CEQ scores is inverse, but the exact curvature might be different based on actual dosage.

The study could have been improved by capturing the route of cannabis administration, capturing the time when cannabis was taken, and evaluating the potential direction of causality, such as whether the cannabis use was a cause or consequence of some specific effects or experiences.

The current study cannot make inferences on the causal effects of cannabis use on subjective experience, and the Bonferroni adjustment does not invalidate the reported results.

Some individuals may use cannabis to alter psychedelic effects, in the same way they may use cannabis to ‘self-medicate’ for psychiatric symptoms.

Conclusions

This study found that concomitant cannabis consumption was dose-dependently associated with higher scores of mystical-type experience, ego-dissolution and visual alterations, and also related to challenging aspects of the psychedelic experience.

The high rates of cannabis use in concert with psychedelic substances may have important implications for harm reduction education and therapeutic use.