The Association of Classic Serotonergic Psychedelic Use and Intention of Future Use with Nature Relatedness

ABSTRACT This study sought to investigate the effects of different substances on nature relatedness (NR) in the general population. An online cross-sectional survey done in Brazil investigated use of ayahuasca/DMT, psilocybe mushrooms, LSD, MDMA/ecstasy, cocaine, cannabis, and alcohol. NR was assessed using the short-form version of the nature related scale (NR-6). One-way analysis of variance (ANOVA) was used to assess group differences between substance naïve-individuals, past users, and current users of each substance. Regression models were used including all the substances and subsequently, sociodemographic variables. ANOVAs with substances which showed significantly higher NR-6 scores in the regression model were used in order to assess the effect of intention of future use on NR. ANOVAs indicated higher NR in users of classic serotonergic psychedelics (ayahuasca/DMT, psilocybe mushrooms, LSD), cannabis, and MDMA/ecstasy. Regression models showed that current use of ayahuasca/DMT and psilocybe mushrooms, and past use of LSD had a positive association with NR. When sociodemographic variables were added, only ayahuasca/DMT past and current use were positively associated with NR. Intention of future use was only significantly associated with NR in individuals who reported intention of future use of psilocybe mushrooms.


Introduction
The last decade has seen the resurgence of research on clinical application of psychedelic substances. The term psychedelic ("psyche" = soul/mind and "delos" = to make visible or clear) is currently applied to different substances with different pharmacological mechanisms of action like lysergic acid diethylamide (LSD), 3,4-methylendioxymetamphetamine (MDMA), ketamine, ibogaine, psilocybin (present in psilocybe genus mushrooms), mescaline, and N-N-dimethyltryptamine (DMT) (present in the Amazonian decoction ayahuasca) (Schenberg, 2018). It can be argued that the term is imprecise since it alludes mostly to the phenomenological/experiential aspects of these substances which are not pharmacologically specific. However, a subclass of these substances is conventionally called classic and/or serotonergic psychedelics and are defined as substances whose main effects are attributable to their serotonin 2A (5HT 2A ) receptor agonistic effects (Carhart-harris and Nutt, 2017;Valle et al., 2016). In this group are included LSD, psilocybin, mescalin and ayahuasca/DMT. The more recent psychedelic research has been focusing mostly on psilocybin and ayahuasca/DMT. Both have been shown effective for treatment-resistant depression in open-label studies Osório et al. 2015;Sanches et al. 2016) and randomized controlled trials against placebo (Davis et al. 2020;Palhano-Fontes et al. 2019). More recently, in a randomized controlled trial, psilocybin showed equivalent results when compared to escitalopram after six weeks of treatment (Carhart-Harris et al. 2021). Psilocybin has also been shown effective in reducing depressive and anxious symptoms in terminal cancer patients (Griffiths et al. 2016) and tobacco cessation (Johnson et al. 2014) and in an open-label study has shown efficacy in obsessive-compulsive disorder (Moreno et al. 2006) and alcohol dependence (Bogenschutz et al. 2015). Evidence also supports that ceremonial ayahuasca use reduces alcohol abuse and tobacco use (Barbosa et al. 2018) and anecdotal evidence suggests efficacy on eating disorders (Lafrance et al. 2017).
Beyond its clinical effects, psychedelics can elicit secondary and long-term effects such as small but significant changes in personality and worldview. A crosssectional study with chronic ayahuasca users showed increased self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality (Bouso et al. 2015), and a long-term prospective study of ayahuasca-naïve subjects found a decrease in reward dependence and increase in novelty-seeking in the 6-month follow-up (Barbosa et al. 2009). An internet survey showed decreases in neuroticism, increases in extraversion, openness among participants that reported psychedelic lifetime use  and in an open-label feasibility study with psilocybin for treatment-resistant depression participants showed decreased authoritarian political views and increased NR (Lyons and Carhart-Harris 2018). Another online survey also found higher scores on openness in classic serotonergic psychedelic users as well lower scores on authoritarian political views and higher NR (Nour, Evans, and Carhart-Harris 2017). Two other internet surveys using English-speaking samples also found increased NR associated with classic serotonergic psychedelic use (Forstmann and Sagioglou 2017;Kettner et al. 2019).
The construct of nature relatedness (NR) captures individual differences in the way people view their relationship with the natural world (Nisbet and Zelenski 2013). It has as theoretical background Wilson's Biophilia hypothesis (Wilson 1984), which argues that since humans evolved in nature, we have an innate need to connect with all life. Increases in NR associated with classic serotonergic psychedelic use have been observed in clinical trials and online surveys (Forstmann and Sagioglou 2017;Kettner et al. 2019;Lyons and Carhart-Harris 2018). NR correlates with happiness (Zelenski and Nisbet 2012), subjective well-being (Nisbet, Zelenski, and Murphy 2011), lower levels of anxiety (Martyn and Brymer 2016), and overall mental and physical health (Dean et al. 2018). Besides effects on mental health, higher NR scores also impact proenvironmental behavior (Forstmann and Sagioglou 2017;Whitburn, Linklater, and Abrahamse 2019) which has become a pressing issue as environmental problems worsen at an ever-increasing pace and human influence in them becomes unequivocal.
The present study analyses the correlation between NR and commonly used substances in Brazil. Considering that polysubstance use is high, this study aims to control for concomitant substance use, an approach used in some (Forstmann and Sagioglou 2017;Nour, Evans, and Carhart-Harris 2017), but not all, studies on the theme. Analyzing substances other than psychedelics can also shed light on what impact these other substances have on NR. The study also aims to analyze if future intention to use a substance is associated with higher NR scores, which is an important gap in current knowledge. To date, there are no published surveys analyzing the association between substance use and NR in a non-English-speaking population. Bridging these gaps with data from a developing country is an important step in advancing knowledge in the field.
Brazil's territory comprises the world's largest rainforest, the Amazon, and other very biodiverse biomes as the Atlantic Forest, the Cerrado and the Pantanal. Since higher NR correlates with pro-environmental behavior it can ultimately have an impact on environmental policies. Environmental conservation in Brazil is fundamental not only to the country itself but to the world at large, hence the importance of assessing how substance use impacts how people view their relationship with the natural world in a Brazilian sample.

Methods
Data used in this study come from an online crosssectional survey in Portuguese language implemented via Survey Monkey and disseminated in Brazil via social media to the public at large. Inclusion criteria were being at least 18 years of age and living in Brazil. The study was approved by the Universidade Castelo Branco's (UBC/ RJ) Ethics Committee. Data collection took place between May 14, 2019 and July 14, 2020.
Measures included sociodemographic data, the Brazilian Portuguese adapted version of the short version of the nature relatedness scale (NR-6) and a substance use questionnaire in which subjects were asked to provide information on previous and current substance use. Substances inquired were: psilocybe mushrooms, ayahuasca/DMT (including both smoked DMT, in its isolated form, and ayahuasca decoction, which contains DMT but also β-carbolines such as harmine, harmaline and tetrahydroharmine), LSD, MDMA/ecstasy, cocaine, cannabis and alcohol. The NR-6 is a single factor, 6-item, 5-point Likert scale (1 = strongly disagree, 5 = strongly agree) whose score is calculated by the average of the answers, with a total score ranging from 0 to 5 (Nisbet and Zelenski 2013).

Statistical analysis
A subset of respondents who fully answered the substance use questionnaire was used in the study. Unadjusted analysis was performed using one-way analysis of variance (one-way ANOVA) corrected by Bonferroni's method comparing NR-6 score of non-users with former users and current users of each substance (ayahuasca/DMT, psilocybe mushrooms, LSD, MDMA/ecstasy, cocaine, cannabis and alcohol).
Adjusted analysis was performed first with a regression model in which all substances contained in the survey were included. Subsequently, sociodemographic variables such as gender, age, ethnicity, educational level, household income and marital status, were added to the regression model.
Substances showing significant NR-6 scores on the regression model went through additional analysis consisting of one-way ANOVAs corrected by Bonferroni's method comparing NR-6 scores between substance-naïve individuals who do not intend to use the substance with substance-naïve individuals who intend to make future use and individuals who report lifetime use of the substance (former + current users). All statistical analyses were performed with STATA version 12.

Results
Respondents (n = 283) were preponderantly women (59.4%) and the most common age bracket was 25 to 34 years old (44.2%). The vast majority declared themselves as white (78.8%) and had a bachelor's degree or higher (70.6%). Concerning household income, about one-third of the sample received 10 to 20 times the minimum monthly wages, while 27.6% received 4 to 10. Those receiving less than two minimum monthly wages accounted only for 13.1%. Most participants were single (62.5%) and about one-third (31.5%) were currently married or in living with a partner (see Table 1).
The most commonly reported currently used substance was alcohol, comprising 75% of the sample and the least was cocaine with only 8%. Concerning past use the most commonly used was cannabis and the least was ayahuasca/DMT. In the classic serotonergic psychedelic category LSD was the most commonly used overall followed by ayahuasca/DMT and psilocybe mushrooms (see Figure 1).

Intention of future use
There were significant differences for ayahuasca/DMT users (F (2, 280) = 22.0, p < .001, η p 2 = .14), with naïve individuals who did not report future intention to use showing similar scores to those who intended to use (p = .136), but those who declared lifetime use of ayahuasca/DMT showing significantly higher NR-6 scores than both groups (p = .001). For psilocybe mushrooms users there were significant differences (F (2, 280) = 13.5, p < .001, η p 2 = .09) with naïve individuals who did not intend to use it showing lower NR-6 scores than both naïve individuals who reported future intention of use (p = .011) and those who reported lifetime use (p < .001), while those who intended to use were no different from subjects with lifetime use (p = .202). Finally, LSD naïve individuals who did not report future intention to use did not show different NR-6 scores from those who intended to use (p = .392), while those who declared lifetime-use of LSD showed significantly higher NR-6 scores than both groups (p = .004 and p = .001, respectively) (F (2, 280) = 9.0, p < .001, η p 2 = .06) (see Figure 3).

Discussion
Past and current users of classic psychedelics (ayahuasca/DMT, psilocybe mushrooms and LSD) had significantly higher NR-6 scores when compared with psychedelic naïve individuals. The same difference was observed in cannabis users, while in MDMA/ecstasy only past users had higher NR-6 scores. Neither alcohol nor cocaine users showed group differences. Regression models indicate that current use of ayahuasca/DMT and psilocybe mushrooms, and past use of LSD showed a positive association with NR-6 scores. When sociodemographic control variables were taken into account only ayahuasca/DMT past and current use was positively associated with NR. Among sociodemographic variables, age higher than 45 and female gender were positively associated with NR, whereas higher household income in general was negatively associated with NR. Intention of future use was only significantly associated with NR in individuals who reported intention of future use psilocybe mushrooms.
Our results are in line with previous research that show a positive association between classic serotonergic psychedelic use and NR. Two cross-sectional surveys found that among different substances, classic psychedelics were uniquely associated with NR (Forstmann and Sagioglou 2017;Nour, Evans, and Carhart-Harris 2017). Nonetheless, in our sample when comparing groups of substance-naïve individuals with past and current users of cannabis the same positive association was also found as well as with MDMA/ecstasy former users. However, in the regression models, which controlled for concomitant use of substances, results corroborated an association of higher NR with classic psychedelics, but not with other substances.
Previous evidence suggests that the association of psychedelics and NR is bidirectional, meaning that people with higher NR scores are more prone to use classic psychedelics and classic serotonergic psychedelic use is associated with increases in NR. Kettner et al (2019) observed that, in their sample, psychedelic-naïve individuals who intended to have a psychedelic experience scored 15-20% higher in the NR-6 than individuals in a demographically similar sample used by Nisbet and Zelenski (2013) in the first validation study of the scale. Findings from the current study explored if future intention of using psychedelics was also associated with NR, but only individuals who reported intention of future use of psilocybe mushrooms showed higher NR than naïve individuals who did not intend to use, while those intending to use ayahuasca/DMT showed a positive but nonsignificant trend and LSD had means in the other direction, but again with no significant differences. Complementary analysis indicated an association between intention to use psilocybe mushrooms and previous use both of ayahuasca/DMT and LSD, so it is unclear whether increased NR is simply associated with previous use of other psychedelics or if prospective users of psilocybe mushrooms may already score higher in NR.
Changes in attitudes are also mediated by certain aspects of the acute psychedelic experience. Prior research shows that higher ego dissolution inventory (EDI) scores during the experience predicts higher subsequent increases in NR-6 (Kettner et al 2019). Higher EDI scores can be interpreted as a proxy for the intensity of the experience since it is dose-dependent (Nour et al. 2016). In our sample, most participants took ayahuasca in a religious/ceremonial context, while there is no formal ceremonial context with psilocybe mushrooms or LSD for which participants reported most often taking it with friends in other settings or with friends in music festivals. Individuals who report LSD use in the survey might not have taken LSD since the substance is not easily identifiable and most often there is no quality control. Psilocybe mushrooms, however, are more easily identifiable even when ground and capsulated because of their distinctive smell, but reported experiences with mushrooms might include low or micro doses, which are less prone to induce substantial and long-term changes. Ceremonial ayahuasca use can help elicit more intense and immersive experiences since it has a safer setting with sitters that supervise the participants and usually involves use of a fully psychoactive dose.  Brazilian ayahuasca ceremonies usually take place in a natural setting (Santos, 2007) and prior evidence indicates that taking psychedelics in nature also contributes to increases in NR (Gandy et al. 2020). Other aspects of the ritual setting such as addressing the plants as "healers," "teachers" or "embodiments of wisdom," and a cultivation of a sense of humility and connectedness could provide a particular framing of such experiences, which potentially impacts participants' environmental relations (Harms 2021). These factors, among others, could explain why ayahuasca was more positively correlated with NR than other psychedelics. Future studies should take into account effects of setting and expectations as moderators of nature relatedness and other long-term subjective changes.

Limitations
Data used in this study did not specify duration or frequency of use, purity of each substance, or usual amount taken in each occasion of use. Our data also comes from a non-probabilistic sample of voluntary responders, and is not representative of the Brazilian population. The two upper levels of the income distribution (classes A and B) are overrepresented in our sample accounting for 47.7% of participants, while they only represent 13% of the Brazilian population (IBGE 2019). People self-declared as white are also overrepresented in the sample (78.8%) not corresponding to their distribution in the population (47.7%) (IBGE 2010). In addition, the sample is younger and more educated than the average population. This sampling bias may be linked not only to internet access, but also substance use in Brazil. Psychedelic substance users could also be overrepresented as well, since they are more keen than other substance users to talk about their experiences due to the more positive public image that these substances have been having in recent years. In our analysis, ayahuasca/ DMT grouped together users of both ayahuasca (decoction taken orally) and isolated DMT (smoked) to increase statistical power. Even though the main active ingredient (DMT) in both forms is the same, they can elicit considerably different experiences with ayahuasca having a ritualized use and considerably longer effects, especially when multiple doses are used in a single ceremony. DMT, however, is not typically used ceremonially and its acute effects usually are short-lived (Timmermann et al. 2018).

Conclusion
In line with previous research, our findings show a positive association between classic psychedelics and NR. Our data also supports the same association with cannabis use and MDMA use. When controlling for concomitant substance use only classic psychedelics showed this association and when sociodemographic control variables were considered only ayahuasca/ DMT, both past and current use, showed significantly higher NR scores. Intention to make future use of a substance was only significantly associated with NR in individuals who reported intention to use psilocybe mushrooms in the future.
Having this association replicated in a middleincome country and non-English-speaking sample further corroborates the body of research that indicates that classic serotonergic psychedelic use is associated with how people relate to the natural world. A note of caution, however, needs to be made. Although the current study supports potential beneficial effects of classic psychedelics in NR, the relationship established between our species and the natural world is mediated by many other variables. Acknowledging the limits of the action of psychedelics and the complexity of our relationship with nature is crucial for future approaches of this issue.

Disclosure statement
No potential conflict of interest was reported by the authors.