Behavioral effects of α,α,ß,ß-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor.

RATIONALE: Ayahuasca is a psychoactive tea prepared from a combination of plants that contain a hallucinogenic tryptamine and monoamine oxidase inhibitors (MAOIs). Behavioral pattern monitor (BPM) experiments demonstrated that the combination of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and a behaviorally inactive dose of an MAO(A) inhibitor such as harmaline or clorgyline induces biphasic effects on locomotor activity in rats, initially reducing locomotion and then increasing activity as time progresses. OBJECTIVES: The present study investigated whether the biphasic locomotor profile induced by the combination of 5-MeO-DMT and an MAOI is a consequence of a reduction in the rate of 5-MeO-DMT metabolism. This hypothesis was tested using a deuterated derivative of 5-MeO-DMT (α,α,ß,ß-tetradeutero-5-MeO-DMT) that is resistant to metabolism by MAO. RESULTS: Confirming our previous findings, 1.0 mg/kg 5-MeO-DMT (s.c.) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the nonselective MAOI pargyline (10 mg/kg). Administration of 5-MeO-DMT alone, even at doses greater than 1.0 mg/kg, produced only reductions in locomotor activity. Although low doses of α,α,ß,ß-tetradeutero-5-MeO-DMT (0.3 and 1.0 mg/kg, s.c.) produced only hypoactivity in the BPM, a dose of 3.0 mg/kg induced a biphasic locomotor profile similar to that produced by the combination of 5-MeO-DMT and an MAOI. Receptor binding studies demonstrated that deuterium substitution had little effect on the affinity of 5-MeO-DMT for a wide variety of neurotransmitter binding sites. CONCLUSIONS: The finding with α,α,ß,ß-tetradeutero-5-MeO-DMT indicates that the hyperactivity induced by 5-MeO-DMT after MAO inhibition is a consequence of reduced metabolism of 5-MeO-DMT, leading to prolonged occupation of central serotonin receptors. These results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of tryptamine/MAOI combinations.

Sudden death associated with intravenous injection of toad extract.

A 24-year-old male died suddenly following the intravenous injection of what was believed to be the ring-derivate amphetamine 'ecstasy' (MDMA). Toxicological analyses of the victim's blood and the injected material, however, failed to reveal MDMA, but showed instead low levels of bufotenine, a tryptamine derivative alkaloid found in the secretions of various toads. In addition, resibufogenin, cinobufagin and bufalin, bufadienolides that are also found in toad venom, were identified in the injected material. While these substances also occur in certain South American plants, the finding of paracetamol, promethazine and diclofenac would be in keeping with ingredients found in the traditional Chinese herbal product Chan Su that derives from the skin glands and secretions of toads and that is often adulterated with standard pharmaceutical drugs. This case demonstrates the problems that users and sellers may encounter from the unknown composition of street drugs and herbal medicines, and the danger that may be incurred from the injection of such materials. It also shows the difficulties that may be associated with attempting to identify low levels of organic toxins in postmortem specimens necessitating a targeted screening approach guided by information obtained at the death scene.

Urinary excretion of dietary contaminants in horses.

REASONS FOR PERFORMING STUDY: Presence of drugs is completely prohibited in post racing urine samples by most of racing and competition authorities, even if environmental contamination might occur. OBJECTIVES: To assess the daily dose of several contaminants absorbed through the diet that would result in detectable concentrations in urine. METHODS: Caffeine, theobromine, theophylline, atropine, scopolamine, bufotenine, DMT or morphine were administered orally to 6 horses, in different dosages, for 3 days before their urine was sampled for regular anti-doping tests. RESULTS: Theobromine, theophylline, bufotenine and morphine daily intake >10 mg, 2 mg, 10 mg and 200 microg, respectively, by a performance horse, were found to result in detectable urinary concentrations. At the 2 tested doses, atropine (5 and 15 mg) and dimethyltryptamine (3 and 10 mg) were not detected in urine. For caffeine and scopolamine, even the lowest dosage tested (5 mg/horse/day and 2 mg/horse/day respectively) induced detectable concentrations of the molecule in urine. CONCLUSIONS: Horses fed dietary contaminants, even at level much below the effective dosage, may be positive to antidoping urine analysis. Further research is needed to gain more confident results on a daily safe intake for caffeine and scopolamine. POTENTIAL RELEVANCE: Selection of feed materials appears to be of great importance to prevent non voluntary positive result to anti-doping tests.

Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine.

Summarized are psychonautic bioassays (human self-experiments) of pharmañopo--crystalline bufotenine (5-HO-DMT; 5-hydroxy-N,N-dimethyltryptamine; dimethylserotonine), at times combined with harmaline or harmine-via intranasal, sublingual, intrarectal, pulmonary (inhaled vapor) and oral routes. This is done by way of pharmacological modeling of diverse South American shamanic inebriants, principally the snuffs ñopolyopo and cebílhaáj, prepared from seeds of Anadenanthera peregrina var. peregrina and A. colubrina var. Cebil, respectively. Psychoptic (visionary) activity of bufotenine has been established and the 1967 Holmstedt-Lindgren hypothesis of the paricá effect-intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs-has been confirmed by 25 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed, and isolation of bufotenine from Anadenanthera seeds detailed (with one table and eight references).

Opposite effects of intraventricular serotonin and bufotenin on rat startle responses.

Rat startle responses to air puffs were monitored in a stabilimeter during the intraventricular infusion of various doses of 5-hydroxytrptamine (5-HT) or the putative hallucinogenic congener of 5-HT, 5-hydroxy-N, N-dimethyltrytamine (5-HDMT) or saline. Qualitativity opposite effects were observed, with 5-HT producing a dose-dependent decrease in responsivity and 5-HDMT increasing the magnitude of startle responses. No specific effects of either compound could be demonstrated on the presumably separable processes of sensitization and habituation. The results are discussed in the context of a central serotonergic system which facilitates behavioral inhibition and which is antagonized by indoleamine hallucinogens.