Prevalence of reported peyote use 1985-2010 effects of the American Indian Religious Freedom Act of 1994.

BACKGROUND: Peyote was classified as a hallucinogen in the Drug Abuse Control Act of 1965, leaving American Indian (AI) religious use in legal ambiguity. In 1994, the American Indian Religious Freedom Act was amended to unambiguously protect the right of religious use of peyote for AIs. OBJECTIVES: The purpose of this article is to report the prevalence rates of peyote use by AIs compared to the rest of the US population and to determine what effect the act's passage had on peyote use rates. METHODS: This investigation utilized an analysis of existing archived large nationally representative surveys of the American population. Data on peyote use rates was determined for most years 1985 through 2010. A total of 886,088 completed surveys were analyzed, of which 12,749 were from AIs. Use rates were triangulated using peyote harvest data. RESULTS AND CONCLUSIONS: Peyote use for AIs and the rest of the US population has remained stable between 1% and 2%. American Indian use rose dramatically in the 4 years following the AIRFA and leveled to just under 10%. The rapidity of the rise was excessive in light of the growth in the NAC and compared to the amounts of peyote stocks available. It is hypothesized that social desirability biases suppressed the Pre-AIRFA use rates due to peyote illegal status. SCIENTIFIC SIGNIFICANCE: Beyond describing peyote use rates and the effects of the AIRFA, this research adds to the body of evidence regarding the levels of under-reporting of illicit drugs.

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects.

Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lacking. Additionally, its mechanism of action has not been investigated in humans. We used a randomized, double-blind, placebo-controlled, crossover design in 16 healthy subjects (8 women) who received placebo, mescaline (100, 200, 400, and 800 mg), and 800 mg mescaline together with the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg) to assess subjective effects, autonomic effects, adverse effects, and pharmacokinetics up to 30 h after drug administration. Mescaline at doses >100 mg induced dose-dependent acute subjective effects. Mescaline increased systolic and diastolic blood pressure at doses >100 mg, with no difference between doses of 200-800 mg. Heart rate increased dose-dependently. Pharmacokinetics of mescaline were dose-proportional. Maximal concentrations were reached after approximately 2 h, and the plasma elimination half-life was approximately 3.5 h. The average duration of subjective effects increased from 6.4 to 14 h with increasing doses of 100-800 mg mescaline. Nausea and emesis were frequent adverse effects at the 800 mg dose. Co-administration of ketanserin attenuated and shortened acute effects of 800 mg mescaline to become comparable to the 100 and 200 mg doses. There were no ceiling effects of the subjective response within the investigated dose range, but tolerability was lower at the highest doses. These results may assist with dose finding for future research and suggest that acute effects of mescaline are primarily mediated by 5-HT2A receptors.

Examination of Recreational and Spiritual Peyote Use Among American Indian Youth.

OBJECTIVE: Some American Indians legally use hallucinogenic substances as part of religious and spiritual ceremonies. Research to date has either failed to differentiate spiritual versus recreational use or has categorized hallucinogen use in an "other drug" or "illegal drug" category. This approach could contribute to ineffectual models of prevention and treatment intervention and limit understanding of hallucinogen use in American Indian cultures. METHOD: This study is a secondary data analysis of an ongoing epidemiologic and etiologic investigation of substance use among American Indian youth (N = 3,861). Two Firth logistic regression models were run with (a) spiritual peyote use and (b) recreational peyote use as the dependent variables, and grade, sex, 30-day alcohol use, 30-day marijuana use, religiosity, religious affiliation, and cultural identity as predictors, as well as a grade by sex interaction term. RESULTS: Grade, sex, religious affiliation, and the interaction term did not predict either recreational or spiritual peyote use. Thirty-day alcohol and marijuana use predicted both spiritual and recreational peyote use, but the effects were stronger for predicting recreational use. Religiosity and cultural identity predicted spiritual but not recreational use, such that American Indian youth who identified as more religious and identified more strongly with their culture were more likely to report using peyote for spiritual purposes. CONCLUSIONS: Our results suggest that current self-reported use of alcohol and/or marijuana by American Indian youth indicates an increased likelihood of using peyote. In addition, use of Firth logistic regression models proved feasible for analyzing rare events like peyote use.

MDA, MDMA, and other "mescaline-like" substances in the US military's search for a truth drug (1940s to 1960s).

This article describes the context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes from the 1940s to the 1960s. Germans first tested mescaline as a "truth drug" in a military context. In the 1940s, the United States military started testing hallucinogenic substances as truth drugs for interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible "speech-inducing" effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the compounds delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/1954 revealed that some of the "mescaline derivatives" tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. In 1955, the military changed focus to lysergic acid diethylamide (LSD), but some interest in mescaline-like compounds remained for their ability to change mood and habit without interfering with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) whether any of the mescaline derivatives tested were being used operationally.

Psychological and cognitive effects of long-term peyote use among Native Americans.

BACKGROUND: Hallucinogens are widely used, both by drug abusers and by peoples of traditional cultures who ingest these substances for religious or healing purposes. However, the long-term residual psychological and cognitive effects of hallucinogens remain poorly understood. METHODS: We recruited three groups of Navajo Native Americans, age 18-45: 1) 61 Native American Church members who regularly ingested peyote, a hallucinogen-containing cactus; 2) 36 individuals with past alcohol dependence, but currently sober at least 2 months; and 3) 79 individuals reporting minimal use of peyote, alcohol, or other substances. We administered a screening interview, the Rand Mental Health Inventory (RMHI), and ten standard neuropsychological tests of memory and attentional/executive functions. RESULTS: Compared to Navajos with minimal substance use, the peyote group showed no significant deficits on the RMHI or any neuropsychological measures, whereas the former alcoholic group showed significant deficits (p < .05) on every scale of the RMHI and on two neuropsychological measures. Within the peyote group, total lifetime peyote use was not significantly associated with neuropsychological performance. CONCLUSIONS: We found no evidence of psychological or cognitive deficits among Native Americans using peyote regularly in a religious setting. It should be recognized, however, that these findings may not generalize to illicit hallucinogen users.

A comparison of the effect of mescaline on activity and emotional defaecation in seven strains of mice.

1 Mescaline hemi-sulphate (35 mg/kg body weight) was injected intraperitoneally into male mice (Mus musculus) from seven genetically diverse laboratory strains. 2 The effect of mescaline was found by comparison of the emotional defaecation and open field activity of mice after mescaline injection with the performance of the same mice after a subsequent saline (0.9% w/v NaCl solution) control injection. 3 In strains A2G, C3H/He, C57BR/cd, CBA/Cam and F/St, mescaline inhibited emotional defaecation and stimulated open field activity. These effects did not occur in strains 1CFW and Schneider. 4 A positive relationship was found between the degree of emotional defaecation characteristic of each strain in the saline control experiment and the inhibitory effect of mescaline on emotional defaecation. 5 Pre-treatment of mice with tranylcypromine (20 mg/kg body weight, i.p.) had no effect on emotional defaecation or on its inhibition by mescaline.

6-Hydroxydopamine inhibits some effects of mescaline centrally administered to rabbits.

The narcotic antagonist naloxone does not antagonize antinociception elicited in the rabbit by 100 microgram/kg of mescaline centrally administered, whereas pretreatment with 6-hydroxydopamine (6-OHDA) inhibits this mescaline effect. Stereotyped behavior of rabbits following central mescaline administration is also prevented by 6-hda pretreatment. Since 6-OHDA in known to produce a degeneration of catecholamine containing nerve terminals, a crucial role of catecholamines is suggested in the complex of effects seen in the rabbit after central administration of the hallucinogen.

Action of a chronic administration of mescaline in dynamic behavioural situations.

The modifications of the rat behaviour caused by a chronic administration of mescaline were studied in two schedules of operant conditioning. In the "periodic conditioning" test, the schedule of reinforcement was changed from a fixed ratio to a fixed interval schedule. Mescaline (4 mg/kg/day and 10 mg/kg/day) caused no modification of the ability of the rat to adapt its behaviour to the new experimental situation. In the "reversal test" the contingency for food delivery was switched from one lever, where responses were previously reinforced to the other lever where responses had no programmed consequences. A chronic administration of mescaline (4 mg/kg/day) caused a total incapacity of the rat to switch to the lever which became reinforced in the reversal trial. A chronic administration of 9 mg/kg/day of mescaline had an excitatory effect and the number of reinforced responses in the II and III reversals exceeded the unreinforced responses in a measure greater than in the controls.

Mescaline action on "memory decay" and "problem solving" behavior in the rat.

The modifications of behavior caused in the rat by a chronic oral administration of mescaline have been studied in three experimental situations. In the staircase maze mescaline accelerated the spontaneous decay on the conditioned reflex (memory decay) during the period without daily training. Only the results observed at 30 mg/kg/day of mescaline were statistically significant. In a T maze two lateral alleys closed by two swinging doors, 30 mg/kg/day of mescaline increased the time spent in opening the first door. When the two doors of the lateral alleys were closed with a latch, mescaline 30 mg/kg/day, caused an increase in the time spent by the rat in opening the doors. Mescaline caused an increase in food consumption. The increase at 30 mg/kg/day is statistically significant.

GLC-mass spectral determination of mescaline in plasma of rabbits after intravenous injection.

A GLC-mass spectral analysis with a deuterated internal standard was developed to measure plasma mescaline concentrations after intravenous administration to rabbits. The drug and the internal standard were extracted with benzene, derivatized with trifluoroacetic acid anhydride, and chromatographed on 2.5% QF-1 with mass fragmentographic detection. The detection limit is 5 ng/ml of plasma. The relative standard deviation was approximately 5%. The main advantage of this method is that it combines the specificity of the GLC retention time and mass spectral fragmentation pattern with the sensitivity of the mass fragmentographic detection.

Effects of intraocular mescaline and LSD on visual-evoked responses in the rat.

The effects of mescaline and LSD on the flash-evoked cortical potential (FEP) were determined in unrestrained rats with chronically-implanted electrodes. Systemic administration of mescaline or LSD significantly attenuated the primary component of the FEP at three stimulus intensities with the greatest effect observed 60-90 minutes following drug administration. The magnitude and specificity of the effects of these agents on the primary response suggest that they produce deficits in conduction through the retino-geniculato-cortical system. The serotonin receptor antagonists, cyproheptadine and methysergide, antagonized the mescaline-induced depression of the FEP in accordance with neurochemical and behavioral evidence that mescaline acts as a partial agonist on serotonin receptors. Topical or intraocular administration of atropine antagonized the actions of systemically-administered mescaline. In addition, intraocular administration of mescaline or LSD attenuated the FEP indicative of an action of these hallucinogens on visual processing in the retina which is modulated by muscarinic receptor activity.

Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca.

Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950's and 1960's they were largely prohibited in medical treatment and human research starting in the 1970's as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable "after-glow" effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics' well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.