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
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
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
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
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
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.
Drug and alcohol dependence
March 1, 2025
Joseph J Palamar, Jennifer S Jewell, Omar El-Shahawy et al.
9 citations
Reported ketamine poisonings in the US rose from 205 in 2019 to 414 in 2023, the highest in reporting history. Most cases involved ingestion (57.2%) and misuse or abuse (36.2%). The proportion of cases involving suspected suicide attempts doubled from 12.7% to 25.9%, and ingestion increased from 46.0% to 65.2%. Cases with major effects or death decreased from 23.4% to 15.6%. Overall, 18.6% of cases experienced a major event or death, but prevalence was lower for those who inhaled ketamine compared to those who did not. Both medical and recreational use and related adverse events need monitoring, especially as off-label prescribing of take-home oral formulations appears to be increasing.
Drug and alcohol dependence
January 1, 2025
James M Zech, David B Yaden, Grant M Jones
9 citations
Lifetime psilocybin use and past-year LSD use are associated with higher rates of cannabis use disorder (CUD) among U.S. adults. Analyzing nationally representative data from the National Survey on Drug Use and Health (2015–2019, 2021–2022), the study found that people reporting use of these psychedelics had roughly double the risk of meeting DSM-5 criteria for CUD, including moderate-to-severe forms, after accounting for sociodemographic factors. Past-year LSD use also predicted three of eleven specific CUD symptoms among cannabis users. The findings indicate that naturalistic use of certain psychedelics may signal greater risk of maladaptive cannabis use, rather than supporting therapeutic benefits.
Drug and alcohol dependence
May 1, 2024
Joseph J Palamar, Nicole D Fitzgerald, Thomas H Carr et al.
9 citations
Seizures of psilocybin mushrooms by U.S. law enforcement rose sharply between 2017 and 2022, suggesting increasing availability. The number of seizures grew from 402 in 2017 to 1,396 in 2022, a 368.9% increase, with the Midwest accounting for the most seizures (36.0%) and the West next (33.5%). The total weight seized rose from 226.0 kg to 844.0 kg, a 2,749.7% increase; the West had the greatest total weight (1,864.2 kg, 42.6%) followed by the South (1,831.9 kg, 41.8%). Significant increases occurred in all four U.S. regions. The authors call for more prevention and harm reduction education.
Drug and alcohol dependence
December 1, 2023
Caryssa R Drinkuth, Michael J Lehane, Gregory C Sartor
9 citations
In oxycodone-dependent male and female mice, a single dose of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) reduced withdrawal behaviors when given 24 hours before naloxone-precipitated withdrawal, and blocked drug-induced reinstatement of oxycodone conditioned place preference when given either 1 or 24 hours beforehand. HNK did not affect locomotion or anxiety-like behavior. The findings suggest that HNK, which lacks ketamine's misuse potential, may be effective in preclinical models of opioid use disorder without producing certain side effects.
Drug and alcohol dependence
May 1, 1978
M Nozaki, D B Vaupel, L D Bright et al.
8 citations
MMDA, a hallucinogenic compound in humans, was compared to LSD in dogs. Single doses of MMDA partially resembled LSD, facilitating the flexor reflex and causing rapid breathing, hyperthermia, and analgesia, but MMDA caused greater pupil dilation. Only LSD consistently triggered a stepping reflex and increased heart rate. In interaction and cross-tolerance studies with LSD-tolerant dogs, MMDA's effects generally differed from LSD's, except for spinal cord facilitation. Cyproheptadine blocked most LSD effects but only MMDA's flexor reflex facilitation. Phenoxybenzamine blocked MMDA-induced pupil dilation, analgesia, and hyperthermia but not LSD's effects. Cross-tolerance to MMDA occurred only for flexor and skin twitch reflexes. MMDA's appetite-suppressing potency was 16 times less than d-amphetamine. The authors conclude MMDA has primarily amphetamine-like activity with some LSD-like actions.
Drug and alcohol dependence
November 1, 2024
Eric L Sevigny, Sylvia Thyssen, Earth Erowid et al.
5 citations
Between 1999 and 2023, 4719 samples submitted as MDMA to the DrugsData drug checking service were analyzed. While 75% of users expected their sample to contain only MDMA, only 48% actually contained MDMA alone. The proportion of MDMA-only samples declined sharply from 57.4% in 1999 to 15.2% in 2009, then recovered to 56.0% by 2017, and rose more moderately to 74.1% by 2023. Across the 25-year period, 199 unique adulterants were detected. Trends in adulterant prevalence matched those seen in law enforcement seizure data. Although more than half of MDMA samples were misrepresented in some way, MDMA quality has stabilized at relatively high levels in recent years.
Drug and alcohol dependence
April 1, 2024
Yoko Nawata, Tsuyoshi Nishioku, Tsuneyuki Yamamoto et al.
2 citations
Repeated administration of MDMA (10 mg/kg daily for 7 days) to mice impaired their recognition memory during withdrawal, as measured by a novel object recognition task. This impairment was prevented by co-administration of diclofenac, a cyclooxygenase inhibitor. Prostaglandin E2 levels increased in the hippocampus on the first day of withdrawal, but not in the prefrontal cortex or striatum. The findings suggest that activation of the arachidonic acid cascade, particularly in the hippocampus, contributes to recognition memory deficits during MDMA withdrawal. Co-use of cyclooxygenase inhibitors with MDMA may reduce concerns about MDMA-induced memory impairment.
Drug and alcohol dependence
September 12, 2025
Matthijs Blankers, Ruben Van Beek, Desirée Spronk et al.
1 citation
In the three days after using ecstasy/MDMA, young adults who regularly use the drug report a small but significant drop in mental well-being, even after accounting for other substance use, sleep, and baseline depression or anxiety. Cocaine co-use and poor sleep further worsened the effect. No similar drop was seen after use of other common substances. The findings suggest the post-acute mood decline is specifically linked to ecstasy/MDMA, not just party or lifestyle factors.
Drug and alcohol dependence
June 2, 2025
Anna Parisi, Lisa Taylor-Swanson, Jennifer L Stewart et al.
1 citation
People with chronic pain who misuse opioids report lower awareness of internal bodily signals compared to those who take opioids as prescribed. In a study of 372 adults on long-term opioid therapy, lower scores on attention regulation and trusting one's body were linked to higher opioid misuse, even after accounting for pain severity. Among 250 participants at elevated risk, an 8-week mindfulness-based program (MORE) produced greater increases in interoceptive awareness than supportive group therapy, and these increases explained reductions in opioid misuse over nine months. The findings suggest that boosting interoceptive awareness may help reduce opioid misuse.