Drug and Alcohol Dependence
June 17, 2010
Josep María Fábregas, Débora González, Sabela Fondevila et al.
228 citations
Regular ritual use of ayahuasca, a psychoactive Amazonian tea containing N,N-dimethyltryptamine, does not appear to cause the psychosocial problems typical of other drugs of abuse. In two studies comparing ayahuasca users (56 jungle-based and 71 urban-based) with matched controls, users scored significantly lower on the Addiction Severity Index (ASI) Alcohol Use and Psychiatric Status subscales. Jungle-based users had a higher frequency of past illicit drug use, but this had ceased at examination except for cannabis. At one-year follow-up, abstinence from illicit drugs was maintained except for cannabis in the jungle group. ASI differences remained significant for the jungle group but not the urban group. A time-dependent worsening was observed only in the Family/Social relationships subscale in the urban group.
Drug and Alcohol Dependence
November 8, 2006
Débora González, Jordi Riba, José Carlos Bouso et al.
163 citations
Salvia divinorum, a plant containing the potent kappa-opioid receptor agonist salvinorin-A, is increasingly used recreationally outside its traditional Mazatec context. Among 32 recreational users surveyed, smoking the extract was the preferred method. Effects were intense but short-lived, appearing within one minute and lasting 15 minutes or less. Users reported psychedelic-like changes in visual perception, mood, and bodily sensations, along with a marked alteration in the perception of external reality and self, resulting in impaired ability to interact. While some effects resembled those of classical psychedelics, the intense derealization and impairment appear unique to salvia. High scores on both LSD and PCAG subscales of the ARCI support kappa-opioid receptor activation as the underlying mechanism.
Drug and Alcohol Dependence
May 1, 2011
Matthew W Johnson, Katherine A Maclean, Chad J Reissig et al.
134 citations
Salvinorin A, the psychoactive compound in Salvia divinorum, produces rapid, dose-dependent subjective effects that peak at 2 minutes and subside within 20 minutes after inhalation. In a double-blind, placebo-controlled study with 4 healthy hallucinogen-using adults, doses from 0.375 to 21 μg/kg increased ratings of mystical-type experiences and effects similar to classic hallucinogens. Salvinorin A did not significantly raise heart rate or blood pressure. Participants reported intense experiences involving altered spatial orientation, pressure on the body, childhood memories, cartoon-like imagery, and contact with entities. The findings suggest salvinorin A has a unique profile that includes mystical-type effects.
Drug and Alcohol Dependence
January 7, 1999
Karl Jansen
127 citations
MDMA is usually considered non-addictive, but three cases show that dependence criteria can be met in rare instances. Recognizing that MDMA can be addictive in exceptional cases is important because very heavy use may cause lasting neuronal changes. Effective identification and treatment of dependent individuals could reduce this risk. In one case, dependence was linked to self-medication of post-traumatic stress disorder (PTSD).
Drug and Alcohol Dependence
January 15, 2014
E. Dakwar, C. Anerella, Carl L. Hart et al.
125 citations
In a small study of eight cocaine-dependent individuals, ketamine infusions produced mystical-type experiences that helped explain increased motivation to quit cocaine a day later. Participants received two doses of ketamine (0.41 mg/kg and 0.71 mg/kg) and a control drug lorazepam (2 mg) in random order. Ketamine, especially the higher dose, caused significantly stronger mystical-type effects than lorazepam. The intensity of those mystical effects, but not dissociative symptoms, predicted greater motivation to stop using cocaine 24 hours after infusion. The findings suggest that psychological experiences during ketamine treatment may contribute to its anti-addiction benefits, though larger studies are needed.
Drug and Alcohol Dependence
June 1, 2012
Matthew W Johnson, R Andrew Sewell, Roland R. Griffiths
121 citations
Psilocybin frequently causes headache in a dose-dependent manner, with incidence, duration, and severity increasing at higher doses. In a double-blind study with 18 healthy participants given 0, 5, 10, 20, or 30 mg/70 kg of psilocybin, all headaches had delayed onset, were transient, and lasted no more than a day. Headaches were neither severe nor disabling. Possible mechanisms include nitric oxide release. These findings indicate headache is an expected adverse event in both nonmedical use and human research, but should not hinder future psilocybin research.
Drug and Alcohol Dependence
February 1, 2015
Laura Hondebrink, Johanna J Nugteren-Van Lonkhuyzen, Daan van der Gouwe et al.
119 citations
The number of new psychoactive substances (NPS) submitted for analysis in the Netherlands rose from 22 samples in 2007 to 431 in 2013. The most common NPS in 2013 were 2C-B, 4-FA, methoxetamine, and 6-APB. After 2012, more NPS were bought as the drug of choice rather than as adulterants. The Dutch Poisons Information Centre recorded 35 NPS exposures in 2013, most often involving 4-FA, mephedrone, MXE, 2C-B, and 6-APB. Neurological and psychological symptoms such as agitation and hallucinations, along with cardiovascular effects like hypertension and tachycardia, were frequently reported. The authors conclude that NPS availability and use are increasing and can cause pronounced clinical effects, recommending continued monitoring combined with clinical and analytical data.
Drug and Alcohol Dependence
May 15, 2020
R. Yockey, Rebecca A. Vidourek, Keith A. King
111 citations
LSD use among US adults increased 56.4% between 2015 and 2018, based on a national survey of over 168,000 people. The largest proportional increases occurred among adults aged 26–34 (from 19.6% to 31.1%) and 35–49 (from 2.73% to 8.82%). Use also rose among people with a college degree or more (from 18.2% to 31.1%) and among bisexual individuals (from 11.2% to 13.0%). In contrast, LSD use decreased among multi-racial individuals, those with less than a high school education, and those who perceived great risk from drugs. These trends can inform prevention and harm reduction efforts.
Drug and Alcohol Dependence
April 1, 2010
James E Lange, Jason Daniel, Kestrel Homer et al.
85 citations
Salvia divinorum is a potent, short-acting hallucinogenic plant increasingly used by adolescents in the United States, yet its effects have been poorly documented. By systematically observing 34 unedited YouTube videos capturing the entire drug experience, trained raters recorded 42 effects at 30-second intervals. Onset of symptoms was rapid, often within 30 seconds, and effects typically dissipated within 8 minutes. Higher doses were associated with longer effect duration. The observations provide a look at users in a non-laboratory setting, showing impairments and behaviors consistent with a powerful hallucinogen. The study also demonstrates both the feasibility and limitations of using YouTube videos to assess emerging drugs and their effects.
Drug and Alcohol Dependence
April 1, 2008
James E Lange, Mark B Reed, Julie M Ketchie Croff et al.
79 citations
Salvia divinorum, a plant used as a legal hallucinogen in many U.S. states, is becoming more popular among college students. In a survey of 1,516 students at a large public university in the southwestern U.S., 4.4% reported using salvia at least once in the past year. The groups most likely to use salvia were those already at higher risk for drug use: White students, males, fraternity members, and heavy episodic drinkers. The authors call for more research to see if these findings apply elsewhere and to identify any negative effects from the drug.
Drug and Alcohol Dependence
October 1, 2010
Matthew J. Baggott, Earth Erowid, Fire Erowid et al.
78 citations
A survey of 500 individuals who had used Salvia divinorum found that 92.6% typically smoked or vaporized the plant, with acute effects lasting about 14 minutes on average. Most participants (80.6%) said they would use it again, and 38.4% described the experience as unique. On at least one occasion, 25.8% reported persisting positive effects lasting 24 hours or more, often an increased sense of well-being, while 4.4% reported persisting negative effects, most commonly anxiety. These findings suggest that Salvia divinorum may produce subacute improvements in mood, which is unusual for a non-medically used drug.
Drug and Alcohol Dependence
June 3, 2012
Pai-Kai Huang, S. Aarde, D. Angrish et al.
74 citations
Recreational use of the synthetic cathinones mephedrone (4-MMC) and MDPV is increasing, with reports of severe symptoms and deaths, but laboratory research on their effects is limited. In male Wistar rats, MDPV and methamphetamine produced a biphasic pattern of voluntary wheel running—higher activity at low doses and lower activity at the highest dose—while 4-MMC and MDMA caused dose-dependent reductions in activity. These results mirror the drugs' known effects on dopamine and serotonin neurotransmission, suggesting MDPV acts as a typical stimulant and 4-MMC resembles the entactogen MDMA, which may predict different abuse patterns and toxicities.
Drug and Alcohol Dependence
June 1, 2010
Vince Cakic, Jacob Potkonyak, Alex Marshall
73 citations
Smoked DMT is the most common route of administration among recreational users, not ayahuasca. Among 121 Australian participants who had used DMT at least once, 98.3% reported smoking it, while only 30.6% had used ayahuasca. The main reasons for first trying DMT were general interest in hallucinogenic drugs (46.6%) or curiosity about its effects (41.7%), and nearly a third (31.1%) cited possible psychotherapeutic benefits. Increased psychospiritual insight was the most commonly reported positive effect for both smoked DMT (75.5%) and ayahuasca (46.7%), aligning with findings from studies of religious ayahuasca use.
Drug and Alcohol Dependence
February 1, 2022
Christopher R. Nicholas, Julie B. Wang, A. Coker et al.
67 citations
MDMA-assisted therapy for severe PTSD may also reduce hazardous alcohol use without increasing illicit drug use. In a randomized trial, 90 adults with severe PTSD received either MDMA-assisted therapy or placebo plus therapy. Those in the MDMA group showed a greater reduction in alcohol use scores (average decrease of 1.02 points) compared to a slight increase in the placebo group (average increase of 0.40 points). Changes in drug use scores did not differ between groups. The findings suggest MDMA-assisted therapy could serve as an integrated treatment for co-occurring PTSD and alcohol or substance use disorders.
Drug and Alcohol Dependence
July 1, 2012
Raimondo Bruno, Allison J Matthews, Matthew Dunn et al.
58 citations
More than a quarter (28%) of regular ecstasy users in Australia had used an emerging psychoactive substance (EPS) in the past six months, most often a stimulant like mephedrone (17%) rather than a psychedelic like 5-MeO-DMT (13%). Users of stimulant EPS resembled mainstream ecstasy users in demographics and risk behaviors, while psychedelic EPS users were a distinct subgroup who started ecstasy earlier, used more multiple substances (cannabis, inhalants, GHB, ketamine), and experienced more legal, psychological, and social problems. The demographic similarity of stimulant EPS consumers and positive responses to these drugs, combined with declining ecstasy purity, suggest stimulant EPS may expand further into ecstasy markets and pose greater public health risks.
Drug and Alcohol Dependence
May 1, 1999
Cory S. Freedland, Robert S. Mansbach
51 citations
Ayahuasca, a psychoactive plant mixture traditionally used by aboriginal populations for spiritual and medicinal purposes, contains beta-carbolines from the Banisteriopsis caapi vine and the hallucinogen N,N-dimethyltryptamine (DMT). In mice, the beta-carboline harmine and B. caapi extract produced similar behavioral effects, especially in open-field tests, and both decreased acoustic startle amplitude without significantly affecting prepulse inhibition. DMT augmented clonic and tonic motor movements and appeared to attenuate the startle-decreasing effects of harmine and B. caapi, though these effects fell just short of significance. The findings suggest that the behavioral effects of B. caapi are largely due to harmine and related beta-carbolines, indicating the vine directly contributes to ayahuasca's unique subjective effects.
Drug and Alcohol Dependence
December 1, 2015
Johanna J Nugteren-Van Lonkhuyzen, Antoinette J H P van Riel, Tibor M Brunt et al.
48 citations
The number of new psychoactive substances (NPS) on the illicit drug market has increased markedly. Users often perceive their risk as medium or low, but these substances can pose serious health risks and have been linked to drug-related deaths. In Europe, frequently detected NPS include 2C-B, 4-fluoroamphetamine (4-FA), and benzofurans (5-APB/6-APB). A review of existing literature found that the clinical effects of these NPS are comparable to common illicit drugs like amphetamine and MDMA, suggesting that NPS toxicity can be managed using existing treatment guidelines based on clinical effects rather than the specific drug. However, information on health risks is limited to case reports complicated by confounders.
Drug and Alcohol Dependence
June 1, 1998
Gerard J. Marek, George K. Aghajanian
39 citations
Psychedelic hallucinogens fall into three chemical groups: ergolines (e.g., LSD), simple indoleamines (e.g., DMT and psilocybin), and ring-substituted phenethylamines (e.g., mescaline). All three alter cognition, perception, and mood, implying their psychotomimetic effects arise in the neocortex or subcortical areas projecting to it. Evidence suggests that both indoleamine and phenethylamine hallucinogens bind to the 5-HT2A serotonin receptor, and activation of this receptor mediates their psychotomimetic effects. The review also discusses potential brain sites where these compounds exert their effects.
Drug and Alcohol Dependence
September 1, 2016
L J Schep, R J Slaughter, S Galea et al.
30 citations
Ibogaine, an alkaloid from the West African shrub Tabernanthe iboga, is used in the West to treat drug dependence, but requires large, hallucination-inducing doses. Case reports describe ataxia, gastrointestinal distress, ventricular arrhythmias, and sudden deaths in patients. High doses affect neurological receptors and transporters, and rodent studies show neuronal injury in Purkinje cells. Lethality in rodents occurs at about 263 mg/kg orally. Applying safety factors for intra- and inter-species variability and susceptible populations, a safer initial human dose is calculated at 0.87 mg/kg, substantially lower than current practice. Morbidities and mortalities will continue unless practitioners reconsider doses.
Drug and Alcohol Dependence
March 1, 2013
Lawrence P Carter, Chad J Reissig, Matthew W Johnson et al.
28 citations
Acute high doses of dextromethorphan (DXM) impair attention, working memory, episodic memory, and metacognition in healthy volunteers with histories of hallucinogen use. Impairments from 100–300 mg/70 kg DXM were generally smaller than those from 0.5 mg/70 kg triazolam. Doses needed to match triazolam's impairment exceeded 10–30 times the therapeutic dose. Supratherapeutic doses caused impairments on all tasks, indicating a broad therapeutic window for over-the-counter DXM when used appropriately, but relevance to high-dose abuse.
Drug and Alcohol Dependence
March 1, 1978
W R Martin, D B Vaupel, M Nozaki et al.
22 citations
In chronic spinal dogs, several indoleamines and phenethylamines were tested and compared to LSD and amphetamine. Psilocin, mescaline, dimethyltryptamine, and tryptamine acted like LSD. DOM, DOB, DMA, and TMA were mostly LSD-like but had some amphetamine-like effects. PMA and PEA were mainly amphetamine-like with some LSD-like activity. MMDA and MDA showed a mix of LSD and amphetamine properties plus additional unique actions, suggesting other modes of action. Antagonists like phenoxybenzamine and cyproheptadine were used to study effects, and some drugs were also tested in LSD-tolerant dogs and for appetite suppression.
Drug and Alcohol Dependence
February 1, 2013
Cheryl L Currie
19 citations
In a 2008-09 survey of 42,179 Canadian adolescents aged 12-17, 6.2% had used Salvia divinorum in their lifetime and 3.8% in the past year; an estimated 23.2% of users were repeat users. Past-year Salvia use was more common than cocaine or amphetamine use but less common than ecstasy, cannabis, or other hallucinogen use. Use was highest in British Columbia and Quebec. Correlates included older age, male gender, more spending money, binge drinking, illicit drug use, and smoking. Low self-esteem may be a specific correlate. Salvia is readily available and under-regulated, raising public health concerns.
Drug and Alcohol Dependence
October 1, 2022
Otto Simonsson, Simon B. Goldberg, Richard Chambers et al.
16 citations
Among a US-representative sample of 2,822 adults, 613 reported lifetime classic psychedelic use, and 1.5% of those users reported having a seizure while using a classic psychedelic—a rate similar to epilepsy prevalence in the general population. Nearly half of those who had a seizure were also taking antidepressants, mood stabilizers, or opioid replacement therapies at the time. Seizures were more common among respondents with a personal or family history of epilepsy. The findings suggest that classic psychedelic use may elevate seizure risk in certain people, especially those with a personal or family history of epilepsy.
Drug and Alcohol Dependence
May 1, 2000
M H Baumann, R B Rothman, S F Ali
15 citations
Ibogaine, a plant alkaloid, reduces dopamine levels across several brain regions in rats while increasing dopamine metabolites, indicating enhanced dopamine turnover. This effect differs from MK-801, an NMDA antagonist, which does not lower dopamine but modestly raises metabolites in some areas. Both drugs elevate corticosterone, but only ibogaine increases prolactin. The findings suggest ibogaine's in vivo actions on dopamine and neuroendocrine secretion are not solely due to NMDA receptor antagonism.
Drug and Alcohol Dependence
July 1, 2025
Mariana M Prete, Gabriel T B Feitosa, Maria A T Ribeiro et al.
13 citations
Synthetic cannabinoids bind to CB1 and CB2 receptors about 100 times more strongly than natural cannabis, leading to severe clinical effects. A systematic review of 49 studies from 2010 to 2022 found that these drugs primarily harm the neurological and cardiovascular systems, causing seizures, altered consciousness, rapid heart rate, and high blood pressure. Compared to cannabis, synthetic cannabinoids produce more severe cardiovascular and neurological complications. Rare effects include blood clots, immune thrombocytopenic purpura, and psychiatric disturbances. Hospital and intensive care admissions varied widely. The review calls for urgent public health policies and more controlled studies to understand the underlying mechanisms.