OPEN Foundation

Menu
Search
Close this search box.

Safety

Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers from 2005 to 2015

November 28, 2016 / Ayahuasca, Papers, Psychology, Publications, Safety, Toxicology / By / ,

Abstract

Background: Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in β-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia.

Methods: All human exposure calls reported to the American Association of Poison Controls Centers’ (AAPCC) National Poison Data System (NPDS) between September 1, 2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant derived ayahuasca-related product codes. Abstracted data included the following: case age and gender, exposure reason, exposure route, clinical manifestations, treatments given, medical outcomes and fatality.

Results: Five hundred and thirty-eight exposures to ayahuasca botanical products were reported. The majority of the calls to poison control centers came from healthcare facilities (83%). The most common route of exposure was ingestion. Most cases were men (437, 81%, 95% CI 77.7% – 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute. Three hundred thirty-seven (63%) were reported to have a major or moderate clinical effect. The most common clinical manifestations reported were hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%), mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%). There were 28 cases in the series who required endotracheal intubation (5%). Four cases were reported to have had a cardiac arrest and 7 a respiratory arrest. Twelve cases had a seizure. Reports of exposures called to poison centers appeared to increase during this period based on annual estimates. Three fatalities were reported.

Conclusions: Ayahuasca use appears to be rising in the United States based on calls to poison control centers. While most use is reported to be safe and well tolerated, with possible beneficial effects, serious and life threatening adverse manifestations are possible. Most of the exposures reported to poison control centers were young people, more likely to be men and already in a healthcare facility. Further research, which includes comprehensive drug testing, will be needed to better identify the risks and effects of ayahuasca use.

Heise, C. W., & Brooks, D. E. (2016). Ayahuasca exposure: descriptive analysis of calls to US poison control centers from 2005 to 2015. Journal of medical toxicology, 1-4. 10.1007/s13181-016-0593-1

Link to full text

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

November 22, 2016 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Safety / By / , , , , ,

Abstract

Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related side-effects. Future treatment strategies should consider using R-ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

Zhu, W., Ding, Z., Zhang, Y., Shi, J., Hashimoto, K., & Lu, L. (2016). Risks associated with misuse of ketamine as a rapid-acting antidepressant. Neuroscience Bulletin, 32(6), 557-564. 10.1007/s12264-016-0081-2

Link to full text

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

November 17, 2016 / Mushrooms / Psilocybin, Mystical experiences, Other subjects, Papers, Psychology, Publications, Safety / By / , , , ,

Abstract

Acute adverse psychological reactions to classic hallucinogens (“bad trips” or “challenging experiences”), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens.

Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S., Johnson, M. W., & Griffiths, R. R. (2016). The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. Journal of Psychopharmacology, 0269881116678781.
Link to full text

Decision-making in chronic ecstasy users: a systematic review

November 15, 2016 / MDMA, Papers, Psychiatry, Psychology, Publications, Safety / By / , ,

Abstract

Different cognitive impairments have been reported as a result of long-term MDMA/ecstasy use. Increased impulsivity and altered decision-making have been shown to be associated with the development and maintenance of addictive disorders pointing towards the necessity to understand a potential impairment of decision-making due to MDMA use. Thus, assessing the long-term effects of MDMA is crucial in order to evaluate its controversially discussed therapeutic use. The aim of this systematic review is to summarize the scientific literature on potential effects of chronic MDMA use on higher order decision-making processes in humans. Therefore, a systematic search for controlled trials relevant to the topic has been performed. Only studies using specific tasks on decision-making were included that involved subjects in the drug-free interval with drug-naïve, and/or polydrug control groups. A total of twelve studies could be identified that met the inclusion criteria, all of which were cross-sectional studies. The findings on decision-making disturbances in MDMA users were heterogeneous. Seven studies reported increased risky decisions, whereas five studies did not find MDMA-specific influences on decision-making. Increased impulsivity was observed both in MDMA groups and in (poly)drug control groups in almost all studies. Thus, the current state of research does not allow for the conclusion that long-term use of MDMA affects decision-making behavior in general. More detailed specifications as well as further investigations of the relevant processes are needed. Significant tendencies towards risky decision-making among long-term MDMA use have been observed, but need to be confirmed by studies using a longitudinal design.

Betzler, F., Viohl, L., & Romanczuk‐Seiferth, N. (2016). Decision‐making in chronic ecstasy users: a systematic review. European Journal of Neuroscience. 10.1111/ejn.13480
Link to full text

Cognitive and behavioural effects induced by social stress plus MDMA administration in mice

November 10, 2016 / Depression, MDMA, Papers, Psychiatry, Psychology, Publications, Safety / By / , , , ,

Abstract

Adverse life experiences such as social stress may make an individual more vulnerable to drug addiction and mental disorders associated with drug consumption. The present work aimed to evaluate the effects of stress induced by acute social defeat combined with the administration of 3,4-methylenedioxymethamphetamine (MDMA) on depression-like behaviour, memory function and motor response to drug in late adolescent male mice. Two groups of mice were exposed to social defeat (SD) during four encounters with an aggressive co-specific, which took place on alternate days. Immediately after defeat, animals were treated with saline or MDMA 10mg/kg (SD+SAL and SD+MDMA). In control groups, mice were placed in a neutral cage without an opponent (Control+SAL, Control+MDMA). Corticosterone levels and temperature were measured on the last day of this phase. During the following days, the behaviour of the animals was evaluated in the tail suspension test (an animal model of depression), memory tasks (passive avoidance and object recognition) and, after administration of 5mg/kg of MDMA, in the open-field test. Exposure of adult mice to acute social defeat plus MDMA increased immobility in the tail suspension test (depression-like behaviour), produced cognitive impairment, and reduced the motor response to MDMA. An increase in corticosterone levels and a decrease of temperature were also observed. As hypothesised, a combination of social stress and consumption of MDMA increases the risk of developing mental and cognitive disorders. Our results support the idea that stress is a common contributing factor to the high rate of comorbidity between substance abuse and mental disease.

García-Pardo, M. P., Roger-Sánchez, C., Rodríguez-Arias, M., Miñarro, J., & Aguilar, M. A. (2017). Cognitive and behavioural effects induced by social stress plus MDMA administration in mice. Behavioural Brain Research, 319, 63-72. 10.1016/j.bbr.2016.11.012
Link to full text

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction

September 16, 2016 / MDMA, Medicine, Papers, Psychopharmacology, Publications, Safety, Toxicology / By / , , ,

Abstract

BACKGROUND: We present a case of “ecstasy” ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites.

CASE REPORT: A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking “ecstasy” at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels.

CONCLUSION: This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Darracq, M. A., Thornton, S. L., Minns, A. B., & Gerona, R. R. (2016). A Case of 3, 4-Dimethoxyamphetamine (3, 4-DMA) and 3, 4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction. Journal of Psychoactive Drugs, 1-4. 10.1080/02791072.2016.1225324
Link to full text

Ayahuasca Treatment Center Safety for the Western Seeker

September 15, 2016 / Anthropology, Ayahuasca, Ethnobotany, Indigenous use, Papers, Psychology, Psychotherapy, Publications, Safety / By / ,

Abstract

Ayahuasca, an ancient Amazonian psychedelic tea traditionally used ceremonially among indigenous peoples, has recently become known as a possible treatment for a wide range of disorders. The awareness of this sacred medicine has grown exponentially over the past decade, attracting westerners from a wide variety of backgrounds, hoping to find treatment for a myriad of emotional and physical illnesses, as well as spiritual needs. In the wake of the commercialization and westernization of the use of ayahuasca, and the subsequent proliferation of ayahuasca treatment centers, this paper examines the benefits and possible risks of this form of therapy in an effort to create a safety protocol for Westerners in this context. The most practical approach to increasing safety for Westerners attending these Amazonian treatment centers is to educate the seeker prior to treatment and to provide access to specialized therapeutic aftercare services.

Ray, R. R., & Lassiter, K. S. (2016). Ayahuasca Treatment Center Safety for the Western Seeker. Anthropology of Consciousness, 27(2), 121-150. 10.1111/anoc.12060
Link to full text

Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review

September 9, 2016 / Depression, Ketamine, Medicine, Papers, Psychology, Publications, Safety / By / , , ,

Abstract

OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response.

METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication.

RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients.

CONCLUSIONS: In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in attention tests were also predictive to a good response. These predictive factors could be more specific to ketamine. With these different predictor factors (clinical and biological), it could be interesting to develop clinical strategies to personalize ketamine’s administration.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2016). [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review]. L’Encephale. 10.1016/j.encep.2016.06.005
Link to full text

[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Ibogaine for treating drug dependence. What is a safe dose?

September 1, 2016 / Iboga / Ibogaine, Papers, Publications, Safety, Substance Use Disorder, Toxicology / By / , , ,

Abstract

The indole alkaloid ibogaine, present in the root bark of the West African rain forest shrub Tabernanthe iboga, has been adopted in the West as a treatment for drug dependence. Treatment of patients requires large doses of the alkaloid to cause hallucinations, an alleged integral part of the patient’s treatment regime. However, case reports and case series continue to describe evidences of ataxia, gastrointestinal distress, ventricular arrhythmias and sudden and unexplained deaths of patients undergoing treatment for drug dependence. High doses of ibogaine act on several classes of neurological receptors and transporters to achieve pharmacological responses associated with drug aversion; limited toxicology research suggests that intraperitoneal doses used to successfully treat rodents, for example, have also been shown to cause neuronal injury (purkinje cells) in the rat cerebellum. Limited research suggests lethality in rodents by the oral route can be achieved at approximately 263mg/kg body weight. To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). A calculated initial dose to treat patients could be approximated at 0.87mg/kg body weight, substantially lower than those presently being administered to treat drug users. Morbidities and mortalities will continue to occur unless practitioners reconsider doses being administered to their susceptible patients.
Schep, L. J., Slaughter, R. J., Galea, S., & Newcombe, D. (2016). Ibogaine for treating drug dependence. What is a safe dose?. Drug and alcohol dependence, 166, 1-5. 10.1016/j.drugalcdep.2016.07.005
Link to full text