Michael Davis
Psilocybin, the active principle of Psilocybe mexicana, a Mexican mushroom with hallucinogenic properties, is similar to LSD in that it shares the same chemical structural backbone. Both substances are hallucinogens and there appears to be some cross-tolerance between them. Cross-tolerance refers to the generalization of tolerance between distinct chemical entities. In other words, if someone develops a tolerance to one substance, they may also develop a tolerance to another substance that their body perceives as similar. In the case of LSD and psilocybin, studies have shown that patients who develop a tolerance to LSD also develop a cross-tolerance to psilocybin, and vice versa.
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What You'll Learn
Cross-tolerance between LSD and psilocybin
Classical psychedelics, such as psilocybin, mescaline, and lysergic acid diethylamide (LSD), cause a distinct array of changes in affect, perception, and cognitive processes in humans. However, when administered repeatedly within a short period, tolerance to their hallucinogenic effects develops through the gradual accumulation of resistance to their action. This development of tolerance is similar to other psychoactive compounds, such as opioids and cannabinoids, and suggests the occurrence of compensatory homeostatic adaptations following repeated drug administration.
Cross-tolerance to classical psychedelics, or the generalization of tolerance between distinct chemical entities, has been documented for psilocybin, mescaline, and LSD. The development of cross-tolerance between LSD and psilocybin suggests that these two drugs cause psychic disturbances by acting on some common mechanism or a common final pathway. This is further supported by the fact that psilocybin, like LSD, is categorized as a particular type of hallucinogen called an indoleamine, and they both produce similar subjective effects and induce cross-tolerance.
In experiments, the development of "direct" tolerance to LSD was measured after volunteers were administered increasing doses of LSD over several days. The same patients then received psilocybin in increasing doses over several days. The development of "cross" tolerance to psilocybin in patients "directly" tolerant to LSD was then measured by "challenging" the patients, after they had received LSD chronically, with a dose of psilocybin. Similarly, "cross" tolerance to LSD was evaluated by challenging patients, after they had received psilocybin chronically, with a dose of LSD.
In these experiments, a high degree of "direct" tolerance to LSD was observed, and patients "directly" tolerant to LSD were also "cross" tolerant to psilocybin. While definite "direct" tolerance also developed after chronic administration of psilocybin, the degree of "direct" tolerance to psilocybin was less than the degree of "direct" tolerance to LSD. Patients chronically treated with psilocybin were also "cross" tolerant to LSD.
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Psilocybin's effects on the human psyche
Psilocybin is a classic psychedelic with a chemical structure similar to LSD and mescaline. It is found in a variety of mushrooms, with the most potent being Psilocybe mexicana. Psilocybin's effects on the human psyche are similar to those of LSD and mescaline, and cross-tolerance has been observed among these three hallucinogens.
Psilocybin impairs thalamic sensory gating, resulting in an inability to screen out extraneous stimuli and difficulties attending to appropriate stimuli. This overwhelms frontal organizational capacities and is thought to contribute to the observed psychotomimetic effects, such as abnormal mental states, feelings of strangeness, difficulty in thinking, anxiety, altered sensory perception, hallucinations, and alterations of body image.
The serotonin hypothesis of schizophrenia is partly based on the psychotomimetic effects of psilocybin. Psilocybin, like other serotonergic hallucinogens, alters mood, perception, and cognition. Changes in emotion, consciousness, perception, and thought typically begin within 20-30 minutes of ingestion and peak in 30-50 minutes.
Psilocybin-containing mushrooms may also contain phenylethylamine, which may contribute to sympathomimetic effects. In addition, psilocybin increases dopamine transmission in the striatum, possibly through secondary increases in dopamine.
Cross-tolerance between LSD and psilocybin has been demonstrated in experiments where subjects developed tolerance to LSD and were then "challenged" with psilocybin, and vice versa. This cross-tolerance suggests that these drugs cause psychic disturbances by acting on some common mechanism or pathway.
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Cross-tolerance in mice
In one study, mice were administered LSD (lysergic acid diethylamide) every day for four days, and the HTR was observed on the first and fourth days. The results showed that previous administration of LSD significantly affected the HTR, indicating the development of tolerance. Furthermore, cross-tolerance was observed between LSD and another psychedelic substance, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). Mice that were repeatedly administered DOI showed a reduced HTR when induced by other psychedelic substances, such as 2C-T7 or DPT.
Another study examined the effects of pretreatment with the 5-HT2AR antagonist M100907 on the development of tolerance to HTR induced by DOI. The results showed that this pretreatment reduced the acute manifestation of DOI-induced HTR and also prevented the development of tolerance. Additionally, cross-tolerance was observed between DOI and LSD, where repeated administration of one substance reduced the ability of the other to induce HTR.
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Psilocybin and LSD's psychic disturbances
Psilocybin and LSD are both hallucinogens, or psychedelics, that cause changes in perception, thoughts, and feelings. They are also known to induce mystical experiences, such as visions or blending of the senses. For example, a person may smell sounds or hear colours.
Psilocybin is found in certain types of mushrooms, often referred to as "magic mushrooms" or "shrooms". These mushrooms are typically found in the tropical and subtropical regions of the United States, Mexico, and South America. On the other hand, LSD, or lysergic acid diethylamide, is derived from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains.
Both psilocybin and LSD can cause a range of effects, from heightened sensory awareness to impaired judgment and frightening hallucinations. Some users may experience severe, terrifying thoughts and feelings of despair, fear of losing control, or fear of insanity and death. These negative experiences are often referred to as "bad trips".
The development of "cross-tolerance" between LSD and psilocybin suggests that these two drugs cause psychic disturbances by acting on some common mechanism or pathway. In other words, the fact that a person who has developed a tolerance to one of these drugs may also exhibit tolerance to the other drug implies that they share similar effects on the brain.
In summary, psilocybin and LSD are hallucinogenic drugs that can induce a range of perceptual, cognitive, and emotional changes. Their ability to produce cross-tolerance indicates that they likely cause psychic disturbances through shared mechanisms of action in the brain.
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Cross-tolerance in humans
In the context of acid and mushroom cross-tolerance, the drugs in question are lysergic acid diethylamide (LSD), a classic psychedelic, and psilocybin, the psychedelic compound found in certain mushrooms. Both LSD and psilocybin are serotonergic psychedelics, meaning they act primarily on the serotonin system in the brain, specifically the 5-HT2A receptors.
Research has shown that repeated administration of LSD or psilocybin within a short period leads to the development of tolerance to their hallucinogenic effects. This tolerance occurs due to compensatory homeostatic adaptations in the brain following repeated exposure. Furthermore, cross-tolerance between LSD and psilocybin has been observed in human subjects. In other words, individuals who have developed tolerance to LSD become cross-tolerant to psilocybin, and vice versa.
This cross-tolerance phenomenon suggests that LSD and psilocybin likely act through a common mechanism or pathway in the brain, reinforcing their classification as serotonergic psychedelics. It is important to note that the development of cross-tolerance may have implications for therapeutic settings where psychedelics are used, as well as for recreational users who may unintentionally build up tolerance to one substance while using another.
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Frequently asked questions
Acid mushroom cross tolerance refers to the development of tolerance to the hallucinogenic effects of psilocybin (the active principle of Psilocybe mexicana, a Mexican mushroom with hallucinogenic properties) in patients who are already tolerant to LSD, and vice versa.
Both LSD and psilocybin are classified as psychedelics and hallucinogens. They share a similar chemical structure, with psilocybin being converted into psilocin, which works on the 5-HT(2A) receptor. Repeated administration of LSD or psilocybin within a short period leads to a progressive decrease in the hallucinogenic response and the development of cross-tolerance.
Acid mushroom cross-tolerance can result in abnormal mental states, including feelings of strangeness, difficulty in thinking, anxiety, altered sensory perception, hallucinations, and alterations of body image.
The development of acid mushroom cross-tolerance can vary depending on the individual and the dosage. In some experiments, volunteers developed "direct" tolerance to LSD and psilocybin within 6-13 days of increasing doses. However, the degree of "direct" tolerance to psilocybin was found to be less than the degree of "direct" tolerance to LSD.
