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Foreword Preface Introduction What Are Psychoactive Plants? The Use of Psychoactive Plants Psychoactive Plants and Shamanic Consciousness The Fear of Psychoactive Plants The Study of Psychoactive Plants Psychoactive Plants as Factors in the Development of Culture THE PSYCHOACTIVE PLANTS On the Structure of the Major Monographs The Most Important Genera and Species from A to Z Major Monographs Little-Studied Psychoactive Plants Minor Monographs Reputed Psychoactive Plants Legal Highs Psychoactive Plants That Have Not Yet Been Identified PSYCHOACTIVE FUNGI The Archaeology of Entheogenic Mushroom Cults Cultivating Mushrooms The Genera and Species from A to Z Purported Psychoactive Fungi General Literature on Psychoactive Fungi PSYCHOACTIVE PRODUCTS ACTIVE CONSTITUENTS OF PLANTS Active Plant Constituents and Neurotransmitters The Active Plant Constituents from A to Z Botanical Taxonomy of Psychoactive Plants and Fungi General Bibliography Bibliographies Periodicals Books and Articles Acknowledgments Index
Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.
OBJECTIVE: The authors evaluated the association between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorders in adults with ADHD, attending to comorbidity with mood, anxiety, and antisocial disorders. It was hypothesized that psychiatric comorbidity would be a risk factor for psychoactive substance use disorders. METHOD: Findings for 120 referred adults with a clinical diagnosis of childhood-onset ADHD were compared with those for non-ADHD adult comparison subjects (N = 268). All childhood and adult diagnoses were obtained by structured psychiatric interviews for DSM-III-R. RESULTS: There was a significantly higher lifetime risk for psychoactive substance use disorders in the ADHD adults than in the comparison subjects (52% versus 27%). Although the two groups did not differ in the rate of alcohol use disorders, the ADHD adults had significantly higher rates of drug and drug plus alcohol use disorders than the comparison subjects. ADHD significantly increased the risk for substance use disorders independently of psychiatric comorbidity. Antisocial disorders significantly increased the risk for substance use disorders independently of ADHD status. Mood and anxiety disorders increased the risk for substance use disorders in both the ADHD and comparison subjects, but more demonstrably in the comparison subjects. CONCLUSIONS: Although psychiatric comorbidity increased the risk for psychoactive substance use disorders in adults with ADHD, by itself ADHD was a significant risk factor for substance use disorders. More information is needed to further delineate risk and protective factors mediating the development of substance use disorders in persons with ADHD.
BACKGROUND: Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions. METHODS: We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed. RESULTS: Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups. CONCLUSIONS: An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.
Rest homes have become a major component of the health care system for frail elderly persons and deinstitutionalized psychiatric patients. Although psychoactive medications are frequently used in rest homes, there is little detailed information about the extent of such use, its supervision, or its effects. In a survey of a random sample of 55 rest homes in Massachusetts, we found that 55 percent of the residents were taking at least one psychoactive medication. Antipsychotic medications were being administered to 39 percent; of these, 18 percent were receiving two or more such drugs. In a follow-up investigation, we studied 837 residents in 44 rest homes with particularly high levels of antipsychotic-drug use. About half the residents had no evidence of participation by a physician in decisions about their mental health during the year of the study. A third of the residents had performance deficits on mental-status testing that indicated serious cognitive impairment, although the causal relation of such impairment to medication use could not be determined. Six percent had evidence of moderate or severe tardive dyskinesia, probably as a side effect of medication. An assessment of staff competence revealed a low level of comprehension of the purpose and side effects of commonly used psychoactive drugs. We conclude that psychoactive drugs are widely used in rest homes, with little medical supervision or understanding by staff members of their possible side effects.
The regulation of new psychoactive substances (NPS) has confounded governments throughout the western world. In 2014 the UK government convened an NPS Review Expert Panel to consider a range of approaches. Ultimately the Panel recommended that the government ban all new psychoactive drugs and allow only psychoactive substances specifically exempted, such as alcohol, tobacco and those allowed as medicines. The government introduced the Psychoactive Substances Bill (PSB) in response to that recommendation. Passed in 2016, the Bill has attracted a torrent of criticism from scientists and experts. The Bill could be improved with revision, but the problems of the total ban, as envisioned by the PSB, with respect to the NPS, may be inherent: (1) defining psychoactivity is conceptually fraught, with great consequence for the scope of the prohibition; (2) operationalizing psychoactivity as a usable concept for legal control purposes is extremely difficult, perhaps impossible; and (3) the detachment of penalties for violating a total ban from establishing the harmfulness of a substance is normatively troubling. Given the uncertainties about the effects of a total ban, it is appropriate at this time for other governments to assess more fully the nature of the NPS problem, and the potential control approaches.
To determine whether commonly used psychoactive drugs increase the risk of involvement in motor vehicle crashes for drivers > or = 65 years of age, the authors conducted a retrospective cohort study. Data were obtained from computerized files from the Tennessee Medicaid program, driver's license files, and police reports of injurious crashes. Cohort members were Medicaid enrollees 65-84 years of age who had a valid driver's license during the study period 1984-1988 and who met other criteria designed to exclude persons unlikely to be drivers and to ensure availability of necessary study data. There were 16,262 persons in the study cohort with 38,701 person-years of follow-up and involvement in 495 injurious crashes. For four groups of psychoactive drugs (benzodiazepines, cyclic antidepressants, oral opioid analgesics, and antihistamines), the risk of crash involvement was calculated with Poisson regression models that controlled for demographic characteristics and use of medical care as an indicator of health status. The relative risk of injurious crash involvement for current users of any psychoactive drug was 1.5 (95% confidence interval (CI) 1.2-1.9). This increased risk was confined to benzodiazepines (relative risk = 1.5; 95% CI 1.2-1.9) and cyclic antidepressants (relative risk = 2.2; 95% CI 1.3-3.5). For these drugs, the relative risk increased with dose and was substantial for high doses: 2.4 (95% CI 1.3-4.4) for > or = 20 mg of diazepam and 5.5 (95% CI 2.6-11.6) for > or = 125 mg of amitriptyline. Analysis of data for the crash-involved drivers suggested that these findings were not due to confounding by alcohol use or driving frequency.
Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed.
Pure psychoactive drugs and direct routes of administration are evolutionarily novel features of our environment. They are inherently pathogenic because they bypass adaptive information processing systems and act directly on ancient brain mechanisms that control emotion and behavior. Drugs that induce positive emotions give a false signal of a fitness benefit. This signal hijacks incentive mechanisms of "liking" and "wanting," and can result in continued use of drugs that no longer bring pleasure. Drugs that block negative emotions can impair useful defenses, although there are several reasons why their use is often safe nonetheless. A deeper understanding of the evolutionary origins and functions of the emotions and their neural mechanisms is needed as a basis for decisions about the use of psychoactive drugs.
OBJECTIVE: To assess the prevalence of psychoactive substance use disorders (PSUDs) among a large, unselected group of seriously injured trauma center patients, using a standardized diagnostic interview and criteria. DESIGN: Prevalence study. SETTING: A level I regional trauma center. PATIENTS: Trauma center patients fulfilling the following criteria were eligible subjects: aged 18 years or older, admission from injury scene, length of stay of 2 days or longer, and intact cognition. OUTCOME MEASURES: The PSUDs were diagnosed using the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) and were categorized as abuse or dependence and past or current (within past 6 months). The SCID results were analyzed with respect to demographic factors, injury type, and blood alcohol concentration and urine toxicology results, using chi2 and logistic regression techniques. RESULTS: Of the 1220 patients approached for study, 1118 (91.6%) consented. More than half (54.2%) had a diagnosis of a PSUD in their lifetime. Approximately 90% of alcohol and other drug use diagnoses were for dependence and more than 62% were current. Overall, 24.1% of patients were currently alcohol dependent (men, 27.7%; women, 14.7%; P<.001), and 17.7% were currently dependent on other drugs (men, 20.2%; women, 11.2%; P<.001). Current alcohol dependence rates were not associated with race; rates of dependence on other drugs were higher among nonwhites and victims classified with intentional injuries. While 54.3% of blood alcohol-positive patients were currently alcohol dependent and 38.7% of patients with positive urine screening test results for drugs other than alcohol and nicotine were currently drug dependent, 11.7% of blood alcohol-negative and 3.9% of drug-negative patients, respectively, had current diagnoses of dependence on psychoactive substances. CONCLUSIONS: A high percentage of seriously injured trauma center patients are at risk of having current PSUDs. Patients with positive toxicology screening test results and/or positive screening questionnaire responses should be referred for formal evaluation and treatment.
PURPOSE: Psychoactive medications are biologically plausible and potentially modifiable risk factors of delirium. To date, however, research findings are inconsistent regarding their association with delirium. The association between exposure to anticholinergics, benzodiazepines, corticosteroids, and opioids and the risk of delirium was studied. PATIENTS AND METHODS: A total of 261 hospitalized cancer patients were followed up with repeated assessments by using the Nursing Delirium Screening Scale for up to 4 weeks for incident delirium. Detailed exposure to psychoactive medications was documented daily. Strengths of association with delirium were expressed as hazard ratios (HRs) in univariate and multivariate analyses by using Cox regression models. All medication variables were coded as time-dependent covariates. Whenever possible, exposure was computed by using cumulative daily doses in equivalents; dichotomous cutoffs were determined. RESULTS: During follow-up (mean, 8.6 days), 43 patients became delirious (16.5%). Delirium was associated with a history of delirium and the presence of hepatic metastases at admission. Analysis of the effect of medications was performed adjusting for these factors. Patients exposed to daily doses of benzodiazepines above 2 mg (HR, 2.04; 95% CI, 1.05 to 3.97), above 15 mg of corticosteroids (HR, 2.67; 95% CI, 1.18 to 6.03), or above 90 mg of opioids (HR, 2.12; 95% CI, 1.09 to 4.13) had increases in the risks for delirium. We did not observe associations between anticholinergics and risk for delirium. CONCLUSION: Exposure to opioids, corticosteroids, and benzodiazepines is independently associated with an increased risk of delirium in hospitalized cancer patients.
OBJECTIVE: To examine the role of medications with known psychoactive properties in the development of postoperative delirium. DESIGN: Nested case-control study within a prospective cohort study. SETTING: General surgery, orthopedic surgery, and gynecology services at Brigham and Women's Hospital, Boston, Mass. PATIENTS: Cases (n = 91) were patients enrolled in a prospective cohort study who developed delirium during postoperative days 2 through 5. One or two controls (n = 154) were matched to each case by the calculated preoperative risk for delirium using a predictive model developed and validated in the prospective cohort study. MAIN OUTCOME MEASURES: Medication exposures were ascertained from the medical record by a reviewer blinded to the study hypothesis. Exposures to narcotics, benzodiazepines, and anticholinergics were recorded for the 24-hour period before delirium developed in the 91 cases and for the same 24-hour postoperative period for the 154 matched controls. RESULTS: Delirium was significantly associated with postoperative exposure to meperidine (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.5) and to benzodiazepines (OR, 3.0; 95% CI, 1.3 to 6.8). Meperidine had similar associations with delirium whether administered via epidural or patient-controlled routes, although only the epidural route reached significance (OR, 2.4; 95% CI, 1.3 to 4.4; OR, 2.1; 95% CI, 0.4 to 10.7, respectively). For benzodiazepines, long-acting agents had a trend toward stronger association with delirium than did short-acting agents (OR, 5.4; 95% CI, 1.0 to 29.2; vs 2.6; 1.1 to 6.5), and high-dose exposures had a trend toward slightly stronger association than low-dose exposures (OR, 3.3; 95% CI, 1.0 to 11.0; vs 2.6; 0.8 to 9.1). Neither narcotics (OR, 1.4; 95% CI, 0.5 to 4.3) nor anticholinergic drugs (OR, 1.5; 95% CI, 0.6 to 3.4) were significantly associated with delirium as a class, although statistical power was limited because of the high use of narcotics and the low use of anticholinergics in the study population. CONCLUSIONS: Clinicians caring for patients at risk for delirium should carefully evaluate the need for meperidine and benzodiazepines in the postoperative period and consider alternative therapies whenever possible.
BACKGROUND: In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. METHODS: In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. RESULTS: Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the equal environment assumption. CONCLUSIONS: In accord with prior results in studies of women, the family environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
The treatment of individuals with coexisting psychoactive substance abuse and severe psychiatric disorders requires an integration of principles from the mental health and chemical dependency fields. The authors outline a conceptual model for treating dually diagnosed patients that consists of four treatment phases--engagement, persuasion, active (or primary) treatment, and relapse prevention. The components of these phases include case management, group therapy, psychopharmacology, toxicologic screening, detoxification, family involvement, and participation in self-help groups. Due to the high morbidity and mortality associated with dual diagnoses, the authors encourage the development, implementation, and scientific evaluation of integrated treatment models targeted toward this population.
New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.
We reviewed studies measuring unsupervised use of psychoactive substances in schizophrenic and control populations and organized the results by substance class. Despite much variation in their methodologies, these studies broadly agreed that schizophrenic groups' use of amphetamines and cocaine, cannabis, hallucinogens, inhalants, caffeine, and tobacco was significantly greater than or equal to use by control groups consisting of other psychiatric patients or normal subjects. Schizophrenic groups' use of alcohol, opiates, and sedative-hypnotics was significantly less than or equal to use by control groups. We discuss the implications of this nonrandom pattern of drug choice for the hypothesis of substance abuse as a form of self-medication in schizophrenia.
AIMS: To determine the acute lethal toxicity of a range of psychoactive substances in terms of the dose customarily used as a single substance for non-medical purposes. DESIGN AND METHOD: A structured English-language literature search was conducted to identify experimental studies and clinical reports that documented human and non-human lethal doses of 20 abused substances that are distributed widely in Europe and North America. Four inclusion criteria were specified for the reports, and approximately 3000 relevant records were retrieved from search engines at Biosis, Science Citation Index, Google and the National Library of Medicine's Gateway. In order to account for different drug potencies, a 'safety ratio' was computed for each substance by comparing its reported acute lethal dose with the dose most commonly used for non-medical purposes. FINDINGS: The majority of published reports of acute lethal toxicity indicate that the decedent used a co-intoxicant (most often alcohol). The calculated safety ratios varied between substances by more than a factor of 100. Intravenous heroin appeared to have the greatest direct physiological toxicity; several hallucinogens appeared to have the least direct physiological toxicity. CONCLUSIONS: Despite residual uncertainties, the substantial difference in safety ratios suggests that abused substances can be rank-ordered on the basis of their potential acute lethality.
A multi-residue method was developed that allows for the simultaneous determination of psychoactive compounds such as opioids, tranquilizers, antiepileptics (primidone, carbamazepine plus two metabolites),the cocaine metabolite benzoylecgonine, the antidepressant doxepin, as well as the calcium channel blocker verapamil in raw and treated wastewater, surface water, groundwater, and drinking water. After solid-phase extraction with Oasis HLB at neutral pH, the analytes were detected by LC electrospray tandem MS in the positive ion mode. With a few exceptions relative recoveries of the analytes exceeded 70%. The limits of quantification were in the low ng/L range. Matrix effects were compensated by using appropriate deuterated or 13C-15N-labeled surrogate standards. For raw and treated wastewater, concentration factors were lowered to reduce matrix effects. Most analytes (15 of 20) were found in raw and treated wastewater as well as in surface water, and hence, are presumably ubiquitously present in the environment. Antiepileptics, the opium alkaloids morphine and codeine, dihydrocodeine, the two tranquilizers oxazepam and temazepam, the opioid tramadol, doxepin, and verapamil were detected in STP discharges and German rivers at concentrations up to the microg/L range. In drinking water, only carbamazepine, its metabolite 10,11-dihydroxy-10,11-dihydrocarbamazepine, and primidone were present at concentrations up to 0.020 microg/L.
A study of medication use among 850 residents of 12 representative\nintermediate-care facilities in Massachusetts shows that despite the growing\nevidence of the risks of psychoactive drug use in elderly patients, this\npopulation was exposed to high levels of sedative/hypnotic and antipsychotic\ndrugs. Choice of medication within a given class was often suboptimal, and\nthe use of standing versus as-needed orders was often not in keeping with\ncurrent concepts in geriatric psychopharmacology. Additional research is\nneeded to determine how best to improve these patterns of medication use. (KIE\nabstract)
Older drivers have the second highest risk for motor vehicle collisions of any age group, after adolescents. Psychoactive medications may place older drivers at increased risk for injurious motor vehicle collisions. We conducted a population-based matched case-control study of older drivers who were involved in injurious crashes during 1987 and 1988. The 234 cases and 447 controls were members of a large Seattle-based health maintenance organization. Use of anti-depressants and opioid analgesics by older drivers was associated with increased risk for injurious motor vehicle collisions. Compared with non-users, current users of cyclic antidepressants had an adjusted relative risk (RR) of 2.3 [95% confidence interval (CI) = 1.1-4.8]. Opioid analgesic use was also associated with an elevated crash risk (adjusted RR = 1.8; 95% CI = 1.0-3.4). We found no evidence of a dose-related effect with either class of drug. Current use of benzodiazepines or sedating antihistamines had little association with increased risk for injurious collisions.