Psychedelics tolerance

The third criterion that animal systems should demonstrate with respect to the psychedelic trip in man is the observed tolerance to both the mental effects and mydriasis. This appears to be complete after several daily doses and to be lost after 4 days without LSD. With respect to biologic mechanisms, occurrence of acute tolerance in both man and animals (20) poses a problem. Whether tachyphylactic or other processes are entailed remains to be defined. 

At the least, we should more systematically classify those drugs that produce a psychedelic sequence in man and show cross tolerance with LSD with respect to the different receptor systems that apparently rank order these drugs in terms of their potency. Such rank order effects have been noted on molluscan ganglia (35) in the clam heart on excitation of cardiac muscle in liver fluke on glycolysis... 

It is possible that iso-LSD may block LSD effects somewhat and inhibit the cosmic trips that can result from high doses this is however unproven. Nevertheless, the prime reasons for a lack of cosmicity are undoubtedly low doses and the development of tolerance. A single exposure to LSD or other psychedelics may produce an adaptation or tolerance that lasts the rest of your life (seeing the ocean for the first time is not a repeatable experience). Furthermore, as seems to be the case with the active chemical (THC) and its inhibitor (CBD) in marijuana, the presence of the inhibitor may sometimes result in a more pleasant experience. Only careful studies in which varying amounts of iso-LSD are added to LSD will decide the issue. 

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. 

The first assumption was that by taking psychedelic drugs, subjects were rendered less depressed, anxious, guilty, and angry, and more self-accepting, tolerant, deeply religious, and sensually alert. In other words, subjects were not only made more amenable to psychotherapy, but were... 

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. 

BOL-148 is of special interest because it played a considerable role in psychedelic history. BOL-148 differs from LSD-25 by a single bromine atom, which renders it inactive in terms of mental function. Yet it is capable of producing more anti-serotonin activity than LSD, and it also produces some cross-tolerance with LSD. This compound seems to contradict the simple model that the effects of psychedelics are mediated by serotonin. 

All of the psychedelics share these characteristics. The hody develops rapid tolerance to them, so that if you try to take them often, you do not get the results you want. Even people who really like these drugs don t take them every day, and most users save them for special occasions. 

The effects of a ketamine high usually last an hour, but they can last for 4 to 6 hours, and 24 to 48 hours are generally required before the user will feel completely normal again. Effects of chronic use of ketamine may take from several months to 2 years to disappear completely. Low doses (25 to 100 mg) produce psychedelic effects quickly. Large doses can produce vomiting and convulsions and may lead to hypoxia of the brain and muscles 1 g can cause death. Flashbacks may even occur 1 year after use. Long-term effects include tolerance and possible physical and/or psychological dependence. 

---