Hallucinogens, working

ANSWER When we decided to make MBDB we felt the alpha-ethyl would attenuate hallucinogenic activity. Dr. Shulgin made that compound because he was looking at things that had a stimulant effect. He had made it but had not evaluated it at effective doses. After a discussion, he evaluated it in the group of people that worked with him. 

Substituents on the aromatic ring play a critical role in determining whether or not phenalkylamines possess DOM-like activity. Hallucinogenic activity is commonly associated with methoxy-substituted derivatives (Shulgin 1978) for this reason, much of this work has focused on these types of agents. 

The natural prototype for the phenylalkylamines is mescaline (Structure 1), isolated from the peyote cactus (Lophophora williamsii) by Heffter in 1896 (100) and subsequently obtained synthetically by Spath in 1919 (218). Used for many centuries in the form of peyote by Indians in Mexico and the American Southwest (3), it is often referred to as one of the classic hallucinogens, along with psilocybin, psilocin, and LSD. Little structure-activity work was directed toward mescaline or its congeners until 1955, when Peretz et al. (174) reported that a-methyl mescaline (TMA) (8), which represented a hybrid of the structure... 

A variety of constraints during the past 15 years have virtually eliminated experimental work with hallucinogens in man. Most recent human experience occurred during social use. In this chapter, an attempt is made to use both sources of data to provide a current view of the effects of these drugs in man. 

The question as to where the common 5-HT and/or hallucinogen receptor is located is an intriguing one that cannot be answered convincingly at present. An important lead to its eventual characterization comes from the work of Leysen and Tollenaere (51) and Colpaert et al. (22), who describe two selective 5-HT/LSD antagonists, pirenperone and ketanserin. Investigators in our laboratories have confirmed the specificity of these compounds and observed an... 

A great deal of structural modification work has ensued in the subsequent years. At present, however, the level of effort and number of laboratories involved in this area are small compared to that during the 1960s and 1970s, when hallucinogens were a popular topic in the lay media. It will be easiest to describe this work by focusing on specific types of molecular modifications and how they affect activity. 

Other flavones in passionflower (vitexin, coumerin, umbelliferone) have not been well characterized for their neuropharmacological action. Vitexin (derived from millet in one study) was found to have antithyroid properties. The remaining constituents, maltol and harman alkaloids, are present in small quantities and not presumed to contribute to the psychotropic effects (Meier 1995). Harman alkaloids in greater quantities are hallucinogenic and presumed to work through 5-HT receptors (Grella et al. 1998). 

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). 

Further field work in the original home region of these Indians will be necessary for a full understanding of this interesting hallucinogen. Interest in this newly discovered... 

Doctor, our apologies for disturbing your solitude and the local social environment here. We can appreciate your wish to be undisturbed in your work. We are anxious to push on to La Chorrera, and we hope that you will help us arrange bearers here to go with us. Also, we are here with a special purpose. I refer to the Virola hallucinogens that you reported to Schultes."... 

For some reason, in that exotic setting they managed to charm me completely. Whether they were alone or together, I was always willing to pause from my studies to pass the time with them. We became fast friends. Naturally we discussed my work, since it involved hallucinogens they were very interested, being familiar with LSD from their days in the London scene. We also discovered that we had mutual friends in India and that we all loved the novels of Thomas Hardy. It was a very pleasant idyll. 

Salvinorin A (the major active principal of the plant Salvia divinorum) is an extremely powerful consciousness altering compound. In fact it is the most potent naturally occurring hallucinogen thus far isolated. But before would-be experimenters get too worked-up about it, it should be made clear that the effects are often extremely unnerving and there is a very real potential for physical danger with its use. 

Not only is salvinorin A chemically different from other hallucinogens (it is a diterpene not an alkaloid) but its effects are quite different as well. Many people consider the effects less manageable and harder to work with than other entheogens. The majority of people who have had a full blown experience with salvinorin A are reluctant to ever do it again. Anyone choosing to experiment with this compound should always have an alert, clear-thinking sitter present to prevent them from injuring themselves or others. 

Roquet and Ganc reported that the Mazatecs prepared a dose of S. divinorum from 120 pairs of crushed leaves and used the plant only when the mushrooms and morning-glory seeds were not available. Roquet and his associates used the plant twice in their psychiatric investigations of Mexican hallucinogenic plants and stated that they had difficulties in working with it (Roquet, 1972). 

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