Author: Gary Jackson

Psychedelic and Dissociative Drugs National Institute on Drug Abuse NIDA

In conditioned-stimulus olfactory learning, the psychedelic DOI was found significantly to disrupt short-term learning and memory (Johnson et al., 2011). LSD has been tested in flies for its effect on learning and memory, where it also was found to disrupt short-term memory (C. D. Nichols, personal communication). In experiments examining aspects of learning and long-term memory, DOI had no significant effect on acquisition but significantly disrupted consolidation and recall (Johnson et al., 2011).

• Psilocybin is the main psychoactive compound in ‘magic mushrooms.’ After the observation in 1953 in Mexico of ritual practices involving the ingestion of such mushrooms, psilocybin was chemically characterized and synthesized in 1958.
• Lerner and Lyvers (2006) compared users of psychedelic drugs with users of nonpsychedelic drugs and nonillicit drug–using social drinkers.
• Repeated administration of psychedelics leads to a very rapid development of tolerance known as tachyphylaxis, a phenomenon believed to result from 5-HT2A receptor downregulation.
• These findings of Kometer et al. (2015) provide further evidence that decreased ongoing oscillations below 20 Hz, particularly θ/α oscillations, may be a common mechanism of action of psychedelics.
• In a new study by Schmid et al. (2015), LSD (200 μg) was administered orally to 16 healthy subjects in a double-blind, randomized, placebo-controlled, crossover study.

These results support the hypothesis that the 5-HT2A receptor is involved in the modulation of sensorimotor gating. In a subsequent study, infusion of DOI (1.0–5.0 μg/0.5 μl) into the ventral pallidum (VP) disrupted PPI without having effects on startle reactivity (Sipes and Geyer, 1997). By contrast, DOI infusions into the nucleus accumbens, an adjacent area also expressing 5-HT2A receptors, had no effect on PPI or startle reactivity.

Law enforcement seizures of psilocybin mushrooms rose dramatically between 2017-2022

Mild SCI animals had significantly more 5-HT2A receptor immunoreactivity 4 weeks after SCI than did uninjured controls. They further speculate that 5-HT2 receptor modulation of enhanced recruitment of motoneurons in response to afferent input may contribute to locomotor recovery after an incomplete SCI. If these results can be translated to humans, it suggests that administration of a 5-HT2A agonist at the site of a contusional SCI, possibly by intrathecal administration, might promote recovery from the injury. In a subsequent study, Dave et al. (2004a) examined the role of the hippocampus in 5HT2A receptor–mediated head bobs in the rabbit. Rabbits received bilateral injections of DOI into the CA1 region of the hippocampus after either saline pretreatment or hippocampal administration of MDL11939, the selective 5-HT2A antagonist.

The actual incidence of HPPD is not known and depends on the prevalence of use in different countries, but epidemiologic information is scarce. Important examples of these substances include a substance used in ancient India known as Soma, which was highly revered and is frequently mentioned in the Rigveda, with numerous Vedic hymns written in praise of Soma (Wasson and Ingalls, 1971). In the ancient village of Eleusis, outside Athens, for more than 2000 years there was an annual all-night secret ceremony that is believed to have involved ingestion of a hallucinogenic brew known as κψκεον (Wasson et al., 1978). We know almost nothing about the ceremony other than that profound insights about life could be achieved, and it was apparently a treasured once-in-a-lifetime opportunity for any Greek citizen who had not been convicted of murder. The powerful psychologic effect of LSD was accidently discovered in 1943 (Hofmann, 1979a), followed only a decade later in 1953 by the detection of serotonin in the mammalian brain (Twarog and Page, 1953).

F. Effect of Psychedelics on the Locus Coeruleus

Perhaps even more importantly, these studies report remarkable results of efficacy that are unprecedented for CRPD with any available conventional therapies. Unfortunately, neither study has yet been published, so complete details cannot be reviewed here, although I have seen the results. Nonetheless, a preliminary report of the JHU study results was presented at the 2015 Annual Meeting of the American Psychiatric Association; that presentation will serve as the basis for this summary (Griffiths, 2015). One of the most well documented therapeutic effects of LSD, first established in the 1960s, was alleviation of anxiety and depression in acutely ill patients. This research direction received its original impetus from observations by Chicago internist Eric Kast.

Some of these differences are noteworthy; for example, in psilocin, the potency for activating AA release was nearly 30-fold greater than for stimulating PI turnover. The most well understood and recognized signaling pathway mediated by the 5-HT2A receptor is coupling to Gαq, resulting in stimulation of PI-specific PLC (Conn and Sanders-Bush, 1984; Roth et al., 1984). This enzyme hydrolyzes phosphatidylinositol membrane lipids at the sn-3 position, generating inositol-1,4,5-triphosphate and diacylglycerol (Conn and Sanders-Bush, 1986; Williams, 1999). The inositol phosphates lead to release of Ca+2 from intracellular stores and diacylglycerol remains bound to the membrane and activates protein kinase C (PKC). Data for 2005 to 2006 from the Texas Poison Control Centers were reviewed for mushroom exposures (Barbee et al., 2009).