Psilocybin tolerance

Mg/kg LSD is given at 3 hourly intervals with the animals being tested only after the last injection (32). Cross tolerance has been observed to other indole and phenylalkylamine hallucinogens (11). Similar effects were also reported for other hallucinogens (10) with an order of potency that paralleled that seen in humans (2) that is, the (hallucinogenic) -isomer of LSD was about 10 times as potent as psilocybin and 100 times as potent as mescaline (10). 

Abramson, H. A., Rolo, A., Sklarofsky, B., and Stache, J. (1960) Production of cross-tolerance to psychosis-producing doses of lysergic acid diethylamide and psilocybin. J. Psychol., 49 151-154. 

If a psychedelic is taken several days in succession, some degree of tolerance (failure to produce a trip) develops. If a different psychedelic is then taken and this also fails to produce a trip, the two compounds are said to produce cross tolerance, which strongly indicates that they act in the same way and create roughly the same kind of trip. LSD, mescaline, and psilocybin (and probably the... 

Perhaps the only reliable way to identify a psilocybin trip is by its short duration most trips are completely over in six hours or less. THC, DMT, glycolate esters and very likely muscimole probably do not produce cross tolerance with each other or with the LSD-mescaline-psilocybin group, as would be expected from the distinct kinds of trips produced by each of the former compounds. Other than the synthesis of new compounds, the most fertile source of new trips lies in the combination of varying amounts of known psychedelics. 

Psilocybin and psilocin are believed to work through mechanisms similar to LSD and other indole hallucinogens. Similar to LSD, chronic psilocybin in take also down-regulates 5-HT2 receptors, which parallels the development of behavioral tolerance (Buckholtz et al. 1990). 

Unlike LSD, dorsal raphe neurons are insensitive to mescaline, and unlike LSD and psilocybin, mescaline does not down-regulate 5-HT2 receptors (Penington and Reiffenstein 1986 Buckholz et al. 1990). Mescaline also fails to directly inhibit 5-HT neurons (McCall 1982). Some tolerance develops with repeated administration of mescaline, which also shows cross-tolerance with LSD, but not amphetamine (Colasanti and Khazan 1975). 

Cross tolerance has been demonstrated between LSD and mescaline, psilocybin, and psilocin. There seems to be no cross tolerance between LSD and marijuana or amphetamine. These observations are indicative of the structural similarites of the compounds. 

Unlike other drugs, when a frequent user stops taking mescaline, there are no withdrawal symptoms. In other words, peyote does not cause an addiction, or physical dependence on a drug. However, while using mescaline, a tolerance to psychedelics in general will develop, meaning it will take a larger dose for the user to get the same effects. This tolerance carries over if the user switches to other psychedelics such as LSD or psilocybin, but does not last if mescaline use is discontinued. 

Cross-tolerance occurs between LSD, mescaline and psilocybin, but not between this group and the amphetamine type of hallucinogens. This... 

LSD is generally considered cross-tolerant with mescaline but not with psilocybin—meaning that use of LSD a day before taking mescaline will reduce the impact of the mescaline (less tolerance develops if the order of the compounds is reversed). It is well established that LSD is cross-tolerant with itself—self-limiting, in the sense that if a second dose is taken a day later the effects will be considerably diminished. This tolerance endures significantly for three days and does not fully dissipate for a week. Abram Hoffer has remarked that LSD is its own greatest enemy. This feature acts as a control on human abuse of this drug. 

Substantial tolerance can be built up by repeated doses taken in close sequence. In 1961, Dr. Leo Hollister gave psilocybin to a subject on a daily basis for twenty-one days, starting with 1.5 rng. and increasing it to 27 mg. On the twenty-second day, the subject showed hardly any reaction to 15 mg. After a rest of several weeks, however, the same dose produced the normal degree of psychoactivity. 

Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry 2006 67(ll) 1735-40. 

Comprehensive investigations of these substances have long ago proven beyond doubt that psilocybin, mescaline and LSD are not physically addictive, nor do they cause withdrawal S5Tnptoms of any kind. Repeated self-experimentation over long periods of time is rare most long-term users eventually reduce frequency of use due to the nature of these substances that initiate powerful transpersonal processes and facilitate the emergence of personal conflicts. Besides, habitual daily users quickly develop tolerance to the point of being unable to experience any psychoactive effects at all. That is why clinical trials are spaced to allow for intervals of at least one week between repeated applications. 

Flashbacks, or reoccurrence of hallucinogenic effects, have been reported. Persistent psychosis, anxiety, and depression have been described following mescaline use. Tolerance, but not physical dependence, to mescaline s effects has been reported in humans. Additionally, chronic users may demonstrate crosstolerance to the effects of LSD or psilocybin. 

The term cross-tolerance means simply that were any subject rendered tolerant to the psychoptic effects of lsd, psilocybine or psUocine, such that these no longer affected him (taking these drugs 2 or 3 days in succession wiU do this), he would also be tolerant to the efiects of mescaline. 

Isbell, H.S. etal 1961. Cross tolerance between LSD and psilocybin Psychopharmacologia z 147-159. 

The phenomena of tolerance and cross-tolerance among psychotomimetic agents were Intensively studied. A cross-tolerance was observed between LSD and tryptamine or mescaline, °" but not between LSD or mescaline and amphetamine or LSD and DMT.Interoceptive effects Induced by mescaline, psilocybin and LSD were poorly differentiated by the rat. 

---