
While in the short term, psychedelics increase one’s tolerance and cross-tolerance (for a few days), in the long term, they might create a kind of reverse tolerance (also known as drug sensitisation). This is a well-known pharmacological phenomenon, describing people’s increased reaction (positive or negative) to a drug following its repeated use. This effect can occur in users of stimulants such as cocaine or amphetamines. On the other hand, this sensitisation does not occur with benzodiazepines, which only exhibit increased tolerance (drug desensitisation, or weakening of effect) with repeated use.
However, I have not come across research showing that psychedelics can lead to reverse tolerance on a pharmacological level. There is, in contrast, plenty of research on how psychedelic compounds cause short-term tolerance. Some misinformation on psychedelic-induced reverse tolerance exists, such as can be found in this psychology textbook. This text for psychology students claims:
One notable feature of hallucinogens is their persistence. Some amount of these drugs may remain in the body for weeks. If an individual ingests the hallucinogen again during this time period, the new dose of the chemical is added to the lingering amount, creating more profound and potentially dangerous effects. This effect is sometimes called reverse tolerance because the second dose may be less than the first but cause the same or greater effects.
However, this is complete misinformation. Trace amounts of a psychedelic may be detectable in urine for 2–3 days, with the drugs detectable in hair for 90 days. But the body does not contain a ‘dose’ of the drug that a new dose is added to, and which can somehow ‘reactivate’ weeks later, thereby creating a stronger-than-expected experience.
Instead, what may occur is reverse tolerance of a psychological kind. As users become more familiar with the altered states of consciousness induced by psychedelics, they can find it easier to enter those states with lower doses. This may be similar to how experienced shamans can enter a psychedelic state with lower doses than those used by most users. In fact, shamans may be able to obtain similar altered states without the use of any drugs at all, instead using methods like repetitive drumming and dancing. Similarly, psychonauts may find it easier to slip into altered states when meditating or doing psychedelic breathwork.
While only speculation at this point, it appears that many psychonauts could need lower doses of psychedelics once they are able to recognise and intercept the effects of these compounds.
But perhaps what is being referred to as reverse tolerance or increased sensitivity is, in some cases at least, another aspect of set. For example, if you expect a psychedelic experience to be a certain way, then this can increase the likelihood of that type of experience occurring, even if you take a lower dose.
Psychedelic researchers have pointed out this effect of psychedelics (thinking or hoping that something will happen, encouraging that very thing to happen). This can improve treatment outcomes, if this expectation effect is of a positive nature, but it does also mean clinical trial results may be somewhat biased. After all, trial participants (who carry positive or even highly inflated expectations) will know they’re in the drug group once the effects begin to take hold. Once this happens, expectancy effects can help encourage a powerful mystical experience (or perhaps lead to disappointment if such an experience doesn’t occur).
In any case, psychedelics may not cause psychological reverse tolerance but instead create certain expectations in psychonauts, which then influence their subsequent trips. It would be useful, however, to see research into this area. Studies could be carried out that compare the effects of psychedelics for naive users compared to experienced psychonauts. Questionnaires might be used to see what kinds of psychological factors may correlate with differences in subjective intensity between naive and experienced users (if such differences turn out to be statistically significant).
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Human mind always remember as something special the first time of any good or interesting experience,the unkown play a lot games with mind,so will never be the same,every next time .I remember how i prepare my self for travel when i start researching, from find the perfect day to prapare the place or find the place,even the clothes must being my favourites and more times we was more than 3 friends,with tickets ready to hand to travel together,sometimes waiting days to can combine all that together, to start traveling.After many times,the surpise effect,we will loose it and the interesting is less . Like the childhood years, the thoughts of past is not the past is a mix with nostalgia and memories ,if somehow look a video of what really happened and compare it that,with what you remember,would find huge difference, always people say ,for past that then was everything better. We didn’t care where we sleep,to can go next day to work,to pay the bills,all that didn’t stress as,like now, we was a team of boys,mostly, with few moneys ,the persons we did that. And almost nobody use to travel alone. .(I am not wrote about what we found then and now,have to do,but is big theme,and want only to talk for mind games and how the life changes,change and the experience from past and now).Is simple ,think,even the ice creams we was eating when we was young,we think was very more delicius.
And go to present,we care only to know that we have free time to start,we don’t go out find the friends, we like just have a nice experience or make a Inside look, dont want the other people look us at the travelling time,cause have jobs or childrens. We know now ,where the ticket gonna take you ,how long time will take,and how easy or what difficulties will have. We just prepare the lights and music,sometimes we stay and with pyjamas! the stadium is more often our bed,and thats all. For me,is like watch a movie or have a meditation,depend the ticket.And i prefer be alone inside,with my girl ,that she dont take anything,and i have a person of my choice to can communicate and share my experience.
Both situations are good,always remember the days ,where we was 5 or8 or 10 friend’s together,with the logic, first ,take it and look after what we will do(i talk pro internet and smartphones years),ang now total protected and with expirience, i put other targets to my travel. I remember with a nice feeling the past,but is not that i am looking now, and at present time,i am the driver of bus and not the passenger as was younger. The final thought is something win ,something loose.As get older,is not better or worst is just different. Maybe some some changes of chemistry of my body and mind play a role,or the energy i had young(,but i think this is also other topic cause alot things not only age play role in this). So the passenger always have a more unexpected experience, and driver a more controlled experience. I am lucky to have lived both situations and continue….And maybe one day make one trip , which,would can find my old friends and some tickets for a bus with unknow destination ,as passengers !