The current study investigated the effects of concomitant cannabis use on the subjective quality of a psychedelic experience across a spectrum of measures including mystical type, visual, challenging, ego-dissolution and emotional breakthrough domains. We found 39% of participants in the current study used psychedelics together with cannabis, supporting findings also reported by Licht et al. (2012), where a third of survey participants admitted using cannabis together with LSD or psilocybin, either often or always.

We found evidence of more intense mystical-type, ego dissolution and visual experiences in conjunction with cannabis use, as a linearly as a function of cannabis dose. A quadratic relationship was found for challenging experiences, indicating less challenging experiences with low dose cannabis but more challenging experiences with higher doses. No relationship was found between cannabis and experiences of emotional breakthrough. We are mindful not to be too hasty in inferring that cannabis use directly caused these effects and thus will explore different explanations for our findings, including, first, the possibility that cannabis may indeed have had a direct effect.

That the presence of cannabis tended to be associated with more intense psychedelic effects may be because cannabis itself 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 (Tart 1970; Adamec et al. 1976; Barrett et al. 2018). Indeed, cannabis is sometimes classified as an ‘atypical psychedelic’ (Garcia-Romeu et al. 2016), or ‘psychedelic-like’ agent (Szabó et al. 2015). Furthermore, recent studies have shown that the THC blood levels correlate positively with higher scores on 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) (Zaytseva et al. 2019)—a scale that is often used to assess the subjective effects of psychedelics. As with classic psychedelics (Byock 2018; Carhart-Harris et al. 2018b), the subjective action of cannabis can be dependent on the cultural context in which the drug is used (Adamec et al. 1976; Pihl et al. 1979), and varies both across and within individuals (Atakan et al. 2012; Zaytseva et al. 2019) and with the context in which the drug is used (Tart 1970). We attempted to control for these elements in the current study by asking participants specific questions which covered a broad spectrum of factors (‘set’ and ‘setting’, personality structure, mental health history and others) and include those we found relevant as covariates in our final analysis. Although we attempted to assess the cultural context by asking questions about whether the experience took place in a retreat setting or within a shamanic guiding framework, we wish to acknowledge that the study participants were not of specific religious practices, like Santo Daime, who use ayahuasca together with cannabis during religious ceremonies (MacRae 1998), or other specific indigenous groups, which might in consequence limit the implications of our study to practices outside of the mentioned contexts.

While the molecular basis of the synergistic effects between cannabis and psychedelics was not explored in the current study, the obtained results are suggestive of its existence. Despite serotonergic psychedelics and cannabis not inducing cross-tolerance (Isbell and Jasinski 1969) and having seemingly different modes of action, recent studies have brought to attention a potential degree of overlap in receptor targets of both of these drug classes. In rodents, both the lack of 5-HT_2AR and use of 5-HT_2AR antagonist limited the THC-induced cognitive impairment, which is indicative of a functional interaction between the two receptors (Viñals et al. 2015). In addition, the other constituent of cannabis, CBD, has been reported to facilitate 5-H_1A receptor-mediated neurotransmission (Resstel et al. 2009) and in high doses act as an inverse agonist of 5-HT_1AR (Martínez-Aguirre et al. 2020). In human brain, the majority of 5-HT_1AR are located postsynatpically and have a largely inhibitory function over 5-HT_2ARs (Carhart-Harris and Nutt 2017); therefore, an inverse agonist action on this receptor would result in an increase in the serotonergic transmission. Indeed, it has previously been suggested that also endocannabinoids modulate the serotonin system and play a key role in the regulation of brain excitability (Haj-Dahmane and Shen 2011). Other studies reveal increased synaptic 5-HT concentration as a response to CB1 stimulation (Burokas et al. 2014). However, whether increased 5-HT would function synergistically with psychedelics known to directly stimulate the 5-HT_2A receptor (Nichols 2000) has not been addressed yet.