Cannabis Synthetic Cannabinoids Research

K2/Spice, delta-8, novel compounds

180 peer-reviewed studies

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RTHC-07406StrongSystematic Review

Adverse clinical effects associated with the use of synthetic cannabinoids: A systematic review.

Prete, Mariana M · 2025

From 944 studies screened, 49 met inclusion criteria (2010-2022).

RTHC-07483StrongSystematic Review

Novel psychoactive substances and psychosis: A comprehensive systematic review of epidemiology, clinical features, neurobiology, and treatment.

Ricci, Valerio · 2025

Among 85 studies, synthetic cannabinoids showed consistently higher psychosis risk than traditional cannabis (OR 4.4-5.2 for synthetic cannabinoids vs cannabis).

RTHC-03931StrongObservational

Linking in vitro and ex vivo CB1 activity with serum concentrations and clinical features in 5F-MDMB-PICA users to better understand SCRAs and their metabolites.

Janssens, Liesl K · 2022

Serum concentrations of 5F-MDMB-PICA correlated with ex vivo CB1 receptor activation in a sigmoidal relationship.

RTHC-02747StrongObservational

The Public Health Response to a Large Poisoning Outbreak Involving an Illicit Substance: Synthetic Cannabinoids Contaminated With a Long-Acting Anticoagulant Rodenticide, Illinois, March-July, 2018.

Navon, Livia · 2020

From March to July 2018, 174 confirmed and probable cases of severe coagulopathy (bleeding disorder) were identified among synthetic cannabinoid users in Illinois, including 5 deaths.

RTHC-00782StrongSystematic Review

Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications.

Castaneto, Marisol S · 2014

This comprehensive review documented the rapid proliferation of synthetic cannabinoids (SC) as designer drugs since the early 2000s.

RTHC-08372ModerateCross-Sectional

Synthetic Cannabinoid Use and Sports-Related Concussion Risk Among US Adolescents: Implications for School Health Screening and Prevention.

Kalra, Saurabh · 2026

Synthetic cannabinoid use was associated with 48% higher odds of sports-related TBI (AOR=1.48, 95% CI=1.30-1.70), with TBI prevalence of 22.9% among SC users vs.

RTHC-08508ModerateCase Report

Clinical features and sociodemographic characteristics associated with analytically confirmed exposure to MDMB-4en-PINACA.

Moyns, Emma Jayne · 2026

Of 202 presentations involving 163 patients, 81.2% had reduced consciousness, 49% agitation, 30.2% seizures, and four died.

RTHC-08559ModerateSystematic Review

Neurotoxic potential of synthetic cannabinoids' pyrolysis products.

Pita, Filipa · 2026

Synthetic cannabinoids undergo structural changes when heated during smoking, generating novel, frequently unidentified toxicants.

RTHC-08627Moderatenarrative-review

Evidence-based consensus guidelines for the pharmacological management of substance dependence: Recommendations from the British Association for Psychopharmacology.

Sinclair, Julia Ma · 2026

The British Association for Psychopharmacology convened international experts to produce evidence-based consensus guidelines for the pharmacological management of substance dependence across all major drug classes. For cannabis and synthetic cannabinoid dependence, the guidelines revealed a stark gap: no medications have received regulatory approval for treatment.

RTHC-06270ModerateCross-Sectional

Synthetic cannabinoids in e-cigarettes seized from English schools.

Cozier, Gyles E · 2025

Synthetic cannabinoids were detected in 17.4% of all e-cigarette samples seized from schools.

RTHC-06339ModerateReview

Outsmarting generic legislation: 4 years into the cat-and-mouse game of the synthetic cannabinoid receptor agonist market since the Chinese ban in 2021.

Deventer, Marie H · 2025

Ban-evading strategies included: alternative core structures (oxoindolins, oxopyridone, benzoate), linker replacement (acetamide instead of carboxamide), positional switching on conventional cores, adding or removing substituents (bromination, tail-less compounds), and a do-it-yourself synthesis approach where users convert legal tail-less precursors into banned potent SCRAs..

RTHC-06638Moderateretrospective-cohort

5F-AKB48: A synthetic cannabinoid presenting an emerging public health concern in France.

Harmel, Clément · 2025

Among 304 cases reported to French Poison Control Centers, the median age was 16.5 years with a male-to-female ratio of 4.4:1.

RTHC-06732Moderateanimal study

Synthetic cannabinoid receptor agonists exacerbate fentanyl-elicited respiratory depression and confer resistance to naloxone rescue in mice.

James, Jared C · 2025

Co-administration of fentanyl with synthetic cannabinoids (JWH-018 or 5F-ADB-PINACA) exacerbated respiratory depression beyond either drug alone.

RTHC-07123ModerateObservational

In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors.

Mercier, Gabrielle · 2025

Twenty-eight synthetic cannabinoid receptor agonists were evaluated for receptor binding and signaling.

RTHC-07327ModerateReview

Arrhythmias and cannabis use: A comprehensive overview.

Paulraj, Shweta · 2025

Epidemiological data show a significant association between cannabis use and various arrhythmias, particularly atrial fibrillation.

RTHC-07953ModerateReview

Diagnosis and management of cannabis-related emergencies.

Williams, Mollie V · 2025

Emergency departments are seeing increasing cannabis-related visits; management differs significantly between natural cannabis and synthetic cannabinoid presentations, with synthetic products carrying higher risk of severe outcomes..

RTHC-05078Moderatenarrative review

The synthetic cannabinoids menace: a review of health risks and toxicity.

Alzu'bi, Ayman · 2024

Synthetic cannabinoids produce multisystem toxicity through CB1R and CB2R activation plus non-cannabinoid targets (GPR55, GPR18, PPARs, TRPV1).

RTHC-05168Moderateepidemiological

Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to America's Poison Centers.

Burgess, Alice · 2024

There were 5,022 reported cases from 2021-2022, with the rate per 100,000 population increasing 89.1% (from 0.55 to 1.04).

RTHC-05227ModerateAnimal Study

Sex-specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice.

Corli, Giorgia · 2024

First AKB48 injection impaired sensorimotor responses, temperature, analgesia, and breathing more in females than males.

RTHC-05348ModerateObservational

An Internet Snapshot Survey Assessing the sale of Synthetic Cannabinoid Receptor Agonists for use with Electronic Vaping Devices.

Gould, Allon · 2024

62 websites sold 128 SCRA vaping brands.

RTHC-05558Moderatenarrative-review

Renal Outcomes and Other Adverse Effects of Cannabinoid Supplementation.

Młynarska, Ewelina · 2024

CB2 agonists showed therapeutic potential in diabetic nephropathy, chronic kidney disease, and obesity-related kidney dysfunction.

RTHC-05629ModerateAnimal Study

Evidence for enduring cardiac and multiorgan toxicity after repeated exposure to the synthetic cannabinoid JWH-018 in male rats.

Pintori, Nicholas · 2024

Repeated JWH-018 at 0.25 mg/kg for 14 days caused persistent hypothermia, increased blood pressure and heart rate throughout treatment.

RTHC-05695ModerateCross-Sectional

Synthetic cannabinoid identification in cases associated with blue lotus and valerian root vaping products.

Seither, Joshua Z · 2024

90% of seized drug cases mentioning "blue lotus" or "valerian root" contained at least one synthetic cannabinoid.

RTHC-05802Moderateretrospective-cohort

Clinical effects of cannabis compared to synthetic cannabinoid receptor agonists (SCRAs): a retrospective cohort study of presentations with acute toxicity to European hospitals between 2013 and 2020.

Waters, Mitchell L · 2024

Synthetic cannabinoid presentations had significantly higher rates of drowsiness, coma, agitation, seizures, and bradycardia.

RTHC-05846ModerateReview

Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill.

Zawatsky, Charles N · 2024

The CBD-derived cannabinoid market has expanded from delta-8-THC to include potent synthetic cannabinoids with greater agonist activity at CB1 receptors than delta-9-THC.

RTHC-04494ModerateSystematic Review

Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review.

de Oliveira, Mariana Campello · 2023

Across 64 studies (10 original papers and 54 case studies), synthetic cannabinoid use was associated with severe toxicity including death (14 studies), with AB-CHMINACA and MDMB-CHMICA most commonly involved in fatalities.

RTHC-04880Moderatecomparative-study

Aberrant salience in cannabis-induced psychosis: a comparative study.

Ricci, Valerio · 2023

SPICE users had more severe and persistent positive symptoms than THC users and non-users.

RTHC-04881Moderatecomparative-study

First episode psychosis with and without the use of cannabis and synthetic cannabinoids: Psychopathology, global functioning and suicidal ideation and antipsychotic effectiveness.

Ricci, Valerio · 2023

THC users and especially SPICE users displayed more severe positive symptoms than non-users.

RTHC-04922ModerateSystematic Review

Cannabinoids and Brain Damage: A Systematic Review on a Frequently Overlooked Issue.

Scopetti, Matteo · 2023

Cannabinoid consumption is associated with psychiatric disorders, neurocognitive impairment, neurological disorders, and in some cases of acute consumption of synthetic cannabinoids, death.

RTHC-03736ModerateAnimal Study

Metabolites of Synthetic Cannabinoid 5F-MDMB-PINACA Retain Affinity, Act as High Efficacy Agonists and Exhibit Atypical Pharmacodynamic Properties at CB1 Receptors.

Cabanlong, Christian V · 2022

5F-MDMB-PINACA and its metabolite M2 showed nanomolar affinity and high efficacy at CB1 receptors.

RTHC-03773Moderateretrospective-cohort

Trends in hospital presentations following analytically confirmed synthetic cannabinoid receptor agonist exposure before and after implementation of the 2016 UK Psychoactive Substances Act.

Craft, Sam · 2022

SCRAs were detected in 35.7% (224/627) of patients with suspected novel psychoactive substance exposure.

RTHC-03774ModerateCross-Sectional

Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis.

Craft, Sam · 2022

Users reported a mean of 4.4 withdrawal symptoms after 1+ day without SCRAs.

RTHC-04031ModerateReview

Fourth Generation of Synthetic Cannabinoid Receptor Agonists: A Review on the Latest Insights.

Malaca, Sara · 2022

Fourth-generation synthetic cannabinoid receptor agonists have increased CB1 receptor affinity and efficacy compared to previous generations, leading to more potent psychoactive effects and increased adverse reactions including psychosis, hallucinations, self-harm, tachycardia, and deaths..

RTHC-04041ModerateAnimal Study

Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.

Margiani, Giulia · 2022

Adolescent mice acquired JWH-018 self-administration behavior that was specifically reward-driven and blocked by a CB1 antagonist.

RTHC-04076ModerateCross-Sectional

Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services.

Monti, Manuela Carla · 2022

Of 94 samples, 50% contained up to three different synthetic cannabinoids, with MDMB-4en-PINACA most common.

RTHC-04264ModerateRCT

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis.

Theunissen, Eef L · 2022

JWH-018 (average dose 5.52 mg) caused psychedelic effects (altered internal and external perception), dissociative effects (amnesia, derealization, depersonalization), and confusion in healthy participants with no history of mental illness..

RTHC-03031ModerateReview

Pharmacological and Toxicological Effects of Phytocannabinoids and Recreational Synthetic Cannabinoids: Increasing Risk of Public Health.

Bukke, Vidyasagar Naik · 2021

207 synthetic cannabinoid compounds were identified by the EMCDDA from 2008 to 2020.

RTHC-03063ModerateReview

Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists.

Chung, Eun Yong · 2021

SCRAs are the most commonly abused new psychoactive substances worldwide.

RTHC-03126ModerateObservational

Lethal coagulopathy resulting from the consumption of contaminated synthetic cannabinoids: the story of a public health crisis.

Fasih, Anum · 2021

The outbreak affected 174 reported patients and caused 5 deaths.

RTHC-03257ModerateObservational

The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA.

Krotulski, Alex J · 2021

MDMB-4en-PINACA had a potency of 2.47 nM (compared to JWH-018 at 25.3 nM, making it about 10 times more potent) with 239% efficacy.

RTHC-03570ModerateCross-Sectional

Characterizing Trends in Synthetic Cannabinoid Receptor Agonist Use from Patient Clinical Evaluations during Medical Toxicology Consultation.

Tebo, Collin · 2021

Of 124 NPS cases, 86 (69%) involved SCRAs.

RTHC-03574ModerateRCT

Intoxication by a synthetic cannabinoid (JWH-018) causes cognitive and psychomotor impairment in recreational cannabis users.

Theunissen, Eef L · 2021

At 75 microg/kg, JWH-018 impaired motor coordination (CTT), attention (DAT and SST), memory (SMT), lowered speed-accuracy efficiency (MFFT), and slowed response speed.

RTHC-02380ModerateReview

The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review.

Alves, Vera L · 2020

Synthetic cannabinoids are the largest NPS class with 190 substances reported to the EU Early Warning System (2008-2018) and ~280 reported worldwide.

RTHC-02421Moderateprospective-cohort

Concomitant Substance Use Increases the Toxic Effect of synthetic cannabinoid (Bonsai): A Prospective Study.

Beydilli, İnan · 2020

69.4% of patients had concomitant drug intake.

RTHC-02494Moderateretrospective-cohort

Characteristics and circumstances of synthetic cannabinoid-related death.

Darke, Shane · 2020

Causes of death: accidental toxicity (38.2%), natural disease (20%), suicide (10.9%), accidental toxicity with CVD (9.1%), traumatic accident (10.9%).

RTHC-02572ModerateCross-Sectional

Cannabinoid use in psychotic patients impacts inflammatory levels and their association with psychosis severity.

Gibson, Claire L · 2020

While PANSS psychosis scores were similar between groups, cannabinoid-positive patients showed a negative correlation between IL-6 levels and psychosis severity, meaning higher inflammation was associated with lower symptom scores.

RTHC-02573ModerateSystematic Review

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists.

Giorgetti, Arianna · 2020

No reliable toxic or lethal concentration ranges have been established for synthetic cannabinoids.

RTHC-02593ModerateCase-Control

Investigation of DNA damage, oxidative stress, and inflammation in synthetic cannabinoid users.

Guler, E M · 2020

Synthetic cannabinoid users had significantly higher DNA damage, plasma oxidant status, myeloperoxidase activity, and inflammatory markers (IL-1-beta, IL-6, TNF-alpha).

RTHC-02594ModerateCross-Sectional

Predicting factors for non-suicidal self-injury in patients with schizophrenia spectrum disorders and the role of substance use.

Güney, Erengül · 2020

Substance use disorder increased NSSI risk approximately 4-fold.

RTHC-02656ModerateCase Report

Critical Illness Secondary to Synthetic Cannabinoid Ingestion.

Kourouni, Ismini · 2020

Over two years, 30 patients were admitted to the ICU after synthetic cannabinoid use.

RTHC-02838ModerateCross-Sectional

The switch from one substance-of-abuse to another: illicit drug substitution behaviors in a sample of high-risk drug users.

Shapira, Barak · 2020

448 of 592 high-risk drug users (75.7%) reported substituting their preferred drug.

RTHC-02839ModerateCross-Sectional

Recent Use of Synthetic Cannabinoids, Synthetic Opioids, and Other Psychoactive Drug Groups among High-risk Drug Users.

Shapira, Barak · 2020

Of 342 patients in drug dependence treatment, 16.1% reported past-12-month synthetic cannabinoid receptor agonist (SCRA) use and 24.9% reported recent prescription opioid or fentanyl patch use.

RTHC-02869Moderateretrospective-cohort

Cannabis and synthetic cannabinoid exposure reported to the Israel poison information center: Examining differences in exposures to medical and recreational compounds.

Sznitman, Sharon R · 2020

Of 615 cannabinoid poisoning cases, 55% were recreational cannabis, 33% synthetic cannabinoids, and 12% medical cannabis.

RTHC-01906ModerateReview

Review of the many faces of synthetic cannabinoid toxicities.

Alipour, Azita · 2019

Synthetic cannabinoids produced a wide range of severe toxicities including arrhythmias, myocardial infarction, sudden cardiac death, psychosis, suicidal ideation, seizures, acute tubular necrosis, and intracranial hemorrhage.

RTHC-01913Moderateretrospective-cohort

Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity.

Anderson, Sarah Ann R · 2019

Synthetic cannabinoid-only exposure (n=107) was associated with 3.4x higher odds of coma/CNS depression (OR 3.42, 95% CI 1.51-7.75) and 3.9x higher odds of seizures (OR 3.89, 95% CI 1.39-10.94) compared to cannabis-only exposure (n=86).

RTHC-01930ModerateObservational

Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides: Observational case series and management recommendations.

Bahouth, Mona N · 2019

Hematuria was the most common bleeding symptom.

RTHC-02008Moderateretrospective-cohort

Hospital Stay in Synthetic Cannabinoid Users With Bipolar Disorder, Schizophrenia, or Other Psychotic Disorders Compared With Cannabis Users.

Deng, Huiqiong · 2019

Cannabis users had significantly shorter hospital stays (8.02 days) and lower antipsychotic doses than the no-drug group (10.19 days).

RTHC-02053ModerateReview

Synthetic cannabinoid use disorder: an update for general psychiatrists.

Grigg, Jasmin · 2019

Synthetic cannabinoid use is associated with more rapid development of dependence than cannabis, increased psychiatric risks, complex withdrawal syndromes, and serious physical adverse effects including seizures, cardiotoxicity, and death, suggesting a need for more intensive clinical management..

RTHC-02166ModerateCross-Sectional

Synthetic cannabinoid use among college students.

Mathews, Eva M · 2019

7.9% lifetime synthetic cannabinoid use; 16.7% of users considered or visited the ER.

RTHC-02212ModerateSystematic Review

Use of medicinal cannabis and synthetic cannabinoids in post-traumatic stress disorder (PTSD): A systematic review

Orsolini, Laura · 2019

This systematic review gathered everything published through May 2019 on cannabis and synthetic cannabinoids for PTSD.

RTHC-02317ModerateRCT

Neurocognition and Subjective Experience Following Acute Doses of the Synthetic Cannabinoid JWH-018: Responders Versus Nonresponders.

Theunissen, Eef L · 2019

JWH-018 increased heart rate and impaired critical tracking and memory performance overall.

RTHC-02352Moderateretrospective-cohort

Seizures as a complication of recreational drug use: Analysis of the Euro-DEN Plus data-set.

Wolfe, Caitlin E · 2019

Of 23,947 ED presentations, 4.2% involved seizures.

RTHC-01568ModerateAnimal Study

Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility.

Aguilar, David D · 2018

Researchers used a novel rodent model where about 40% of rats carry genetic susceptibility to a schizophrenia-like phenotype.

RTHC-01607ModerateReview

Toxicology of Marijuana, Synthetic Cannabinoids, and Cannabidiol in Dogs and Cats.

Brutlag, Ahna · 2018

As cannabis becomes more accessible through both medical and recreational legalization, pet exposures to cannabis products have increased significantly.

RTHC-01617ModerateRCT

Cluster randomised controlled trial of an online intervention to prevent ecstasy and new psychoactive substance use among adolescents: final results and implications for implementation.

Champion, Katrina E · 2018

Researchers tested a web-based prevention program delivered through school health education classes to 1,126 Australian students across 11 schools.

RTHC-01623ModerateReview

Synthetic and Non-synthetic Cannabinoid Drugs and Their Adverse Effects-A Review From Public Health Prospective.

Cohen, Koby · 2018

Researchers reviewed the epidemiology and health effects of synthetic cannabinoids compared to natural cannabis from a public health perspective.

RTHC-01639ModerateReview

Psychosis and synthetic cannabinoids.

Deng, Huiqiong · 2018

Researchers reviewed the clinical literature on psychotic symptoms following synthetic cannabinoid (SC) use. Multiple clinical reports documented induction of psychotic symptoms after consuming SC products, including both new-onset psychosis in people with no psychiatric history and psychotic relapses in those with prior episodes. The review found that the relationship between SCs and psychosis is more complex than any single chemical component can explain.

RTHC-01685ModerateObservational

Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

Hermanns-Clausen, Maren · 2018

Researchers prospectively studied 44 patients treated in emergency departments after using synthetic cannabinoids, with lab confirmation of AB-CHMINACA and/or MDMB-CHMICA in blood or urine. Based on the Poison Severity Score, poisoning severity was minor in 4 cases, moderate in 31 cases, and severe in 9 cases (20%). The most common neuropsychiatric symptoms were CNS depression (61%), disorientation (45%), generalized seizures (27%), combativeness (18%), and extreme agitation (16%).

RTHC-01694ModerateSystematic Review

Spicing it up - synthetic cannabinoid receptor agonists and psychosis - a systematic review.

Hobbs, Melissa · 2018

Researchers synthesized evidence from 2 toxicology reports, 4 case-control studies, 3 cross-sectional studies, and 15 case reports on synthetic cannabinoid receptor agonists (SCRAs) and psychosis. The toxicology reports identified toxic psychosis and delirium (40%), agitation (10%), and hallucinations (4-7%) as main presenting features.

RTHC-01723ModerateReview

Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes.

Kong, Tae Yeon · 2018

Researchers reviewed the metabolism of 13 prevalent synthetic cannabinoids, mapping which cytochrome P450 (CYP) enzymes, UDP-glucuronosyltransferases (UGTs), and carboxylesterases are responsible for breaking them down. Synthetic cannabinoids are substrates of multiple drug-metabolizing enzymes, meaning these enzymes process and eliminate them from the body. Critically, synthetic cannabinoids also inhibit CYP and UGT enzymes.

RTHC-01880ModerateReview

Cannabinoids: emerging evidence in use and abuse.

Williams, Molly V · 2018

Emergency departments are seeing increasing cannabinoid-related presentations.

RTHC-01359ModerateObservational

The effects of synthetic cannabinoids on executive function.

Cohen, K · 2017

Across two study sites (Hungary and Israel), 38 synthetic cannabinoid users were compared with 43 recreational cannabis users and 41 non-users on computerized cognitive tests. Synthetic cannabinoid users performed significantly worse than both other groups on the n-back task (working memory accuracy), the Stroop task (response speed and accuracy, measuring inhibition), and a free-recall memory task (long-term memory).

RTHC-01390ModerateAnimal Study

Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model.

Grim, T W · 2017

Using pA2 and pKB analyses (quantitative pharmacological methods), researchers determined that the CB1 receptor antagonist rimonabant produced consistent rightward shifts in the dose-response curves of five synthetic cannabinoids (A-834,735D, WIN55,212-2, CP55,950, JWH-073, CP47,497) and THC. The similarity of the rimonabant affinity estimates across all compounds indicates that CB1 receptors, and not other pharmacological targets, largely mediate the central effects of these synthetic cannabinoids (catalepsy, pain relief, and temperature reduction). This is important because some researchers have speculated that the increased dangers of synthetic cannabinoids might be due to non-CB1 targets, but this quantitative analysis suggests their core pharmacological effects operate through the same receptor as THC..

RTHC-01413ModerateReview

Tripping with Synthetic Cannabinoids ("Spice"): Anecdotal and Experimental Observations in Animals and Man.

Järbe, Torbjörn U C · 2017

This review consolidated the scientific literature on "Spice" compounds, synthetic cannabinoids originally designed as research tools that became widely abused recreational drugs. In behavioral assays comparing synthetic cannabinoids to THC, the synthetic compounds generally produced similar effects but often at greater potency or with additional toxicity.

RTHC-01431ModerateReview

Focus on cannabinoids and synthetic cannabinoids.

Le Boisselier, R · 2017

This review provided a state-of-the-art overview of both natural and synthetic cannabinoids, explaining why synthetic versions produce more extreme effects. The key pharmacological difference: THC is a partial agonist at CB1 receptors (it activates them partially), while most synthetic cannabinoids are full agonists (they activate receptors to their maximum).

RTHC-01491Moderateprospective-cohort

Impact of synthetic cannabinoids on the duration of opioid-related withdrawal and craving among patients of addiction clinics in Kazakhstan: A prospective case-control study.

Prilutskaya, Mariya · 2017

Among 193 patients with opioid use disorder undergoing detoxification in Kazakhstan, the 47 who also regularly used synthetic cannabinoids (SCs) experienced significantly longer withdrawal and craving symptoms compared to those who did not use SCs (p < 0.001). The study identified a dose-response relationship: higher SC intake in the past 30 days (p = 0.045), more recent SC use (p = 0.033), longer total duration of SC use (p < 0.001), and higher SC doses (p < 0.001) were all independently associated with longer symptom duration. This was the first prospective study to examine how synthetic cannabinoid use affects the course of opioid withdrawal, revealing that polysubstance use involving SCs creates a more difficult detoxification process..

RTHC-01549ModerateReview

Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health.

Weinstein, Aviv M · 2017

The review compared synthetic cannabinoids to natural cannabis across several dimensions.

RTHC-01555ModerateReview

Strokes are possible complications of cannabinoids use.

Wolff, Valérie · 2017

Researchers compiled 98 cases from the medical literature where stroke occurred in the context of cannabinoid use.

RTHC-01088ModerateReview

The Changing Drug Culture: Emerging Drugs of Abuse and Legal Highs.

Albertson, Timothy E · 2016

This review for family practitioners cataloged the expanding landscape of synthetic recreational drugs.

RTHC-01131ModerateReview

Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

Cooper, Ziva D · 2016

This review addressed both acute toxicity and the less-discussed problem of dependence and withdrawal from synthetic cannabinoids (SCs). While case reports and media coverage focus on severe acute toxicity, the review highlighted that daily SC use resulting in dependence and withdrawal is a significant and often overlooked concern.

RTHC-01210ModerateObservational

Presentations due to acute toxicity of psychoactive substances in an urban emergency department in Switzerland: a case series.

Liakoni, Evangelia · 2016

Over one year at a Swiss university hospital, researchers systematically tracked every emergency department visit related to recreational drug toxicity.

RTHC-01214ModerateReview

International trends in spice use: Prevalence, motivation for use, relationship to other substances, and perception of use and safety for synthetic cannabinoids.

Loeffler, George · 2016

This review compiled data from nationally and regionally representative surveys worldwide to characterize synthetic cannabinoid (Spice) use patterns. Lifetime prevalence in the general population ranged from 0.2% to 4%.

RTHC-00802ModerateObservational

Detection of new psychoactive substance use among emergency room patients: results from the Swedish STRIDA project.

Helander, Anders · 2014

The STRIDA project monitored new psychoactive substance (NPS) use among patients presenting to Swedish emergency departments and intensive care units.

RTHC-00877ModerateReview

Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential.

Tai, Sherrica · 2014

The review highlights a critical pharmacological difference between natural THC and synthetic cannabinoids: THC is a relatively weak partial agonist at CB1 receptors, while the majority of synthetic cannabinoids are full agonists with higher binding affinity.

RTHC-00408ModerateObservational

Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds.

Dresen, Sebastian · 2010

Researchers analyzed over 140 samples of "herbal incense" products (marketed as legal cannabis alternatives) between June 2008 and September 2009. Initially, products contained CP-47,497-C8 and JWH-018.

RTHC-08169Preliminarynarrative-review

Semi-synthetic cannabinoids: Recent developments, analytical challenges and strategic responses.

Christie, Rachel · 2026

Since hexahydrocannabinol (HHC) first appeared in Europe in late 2022, the semi-synthetic cannabinoid market has expanded rapidly.

RTHC-08296PreliminaryCase Report

Dissociative-like Neurotoxicity Following Analytically Confirmed Exposure To Hexahydrocannabinol (HHC).

Greene, Shaun L · 2026

In this individual case, a 32-year-old man developed a dissociative-like neurologic syndrome plus gastrointestinal symptoms after ingesting a single gummy sold as a THC product.

RTHC-08618PreliminaryObservational

Behavioral pharmacology of novel synthetic indazole, indole, and benzimidazole cannabinoids in rodents.

Shetty, Ritu A · 2026

The DEA identified 11 synthetic cannabinoids of concern, and researchers tested each one in rodent models for two key properties: how strongly they suppressed movement (locomotor depression) and whether rats trained to recognize THC also recognized these compounds (drug discrimination). In locomotor tests, most of the 11 compounds were more potent than THC (which had an ED50 of 3.3 mg/kg).

RTHC-08661PreliminaryObservational

Fast and reliable in vitro activity-based detection of synthetic cannabinoid receptor agonists in e-liquids.

Timmerman, Axelle · 2026

Researchers applied a cell-based activity screening method (CB1/β-arrestin2 recruitment assay using the NanoBiT principle) to detect synthetic cannabinoid receptor agonists (SCRAs) in e-liquids — the first time this approach was used on a real patient case. When applied to an e-liquid from an intoxicated patient, the assay demonstrated strong cannabinoid activity, confirming the presence of SCRAs.

RTHC-08665PreliminaryAnimal Study

Administration of the Synthetic Cannabinoid WIN55,212-2 Increases BDNF Expression Levels in the Adolescent Rat Brain.

Torres, Alejandro Guadalupe · 2026

Adolescent male rats received the synthetic cannabinoid WIN55,212-2 (a dual CB1/CB2 receptor agonist) via injection every 48 hours from postnatal day 30 to 44 — corresponding to human adolescence.

RTHC-08692PreliminaryCase Report

4F-MDMB-BICA toxicity: a fatal case and literature review of synthetic cannabinoid fatalities.

von Both, Ingo · 2026

Toxicology identified 4F-MDMB-BICA and its metabolite in blood, vitreous fluid, and urine.

RTHC-06267PreliminaryCase Report

An Outbreak of Synthetic Cannabinoid-Adulterated Tianeptine Products in New Jersey - Case Series.

Counts, Christopher J · 2025

Products marketed as containing tianeptine were found to contain the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA.

RTHC-06271PreliminaryCase Report

Detection and quantification of synthetic cannabinoids in seven illicitly sourced disposable vapes submitted by an individual presenting to a UK drug and alcohol service.

Craft, Sam · 2025

All seven samples contained 5F-MDMB-PICA at a median concentration of 0.85 mg/mL (range 0.59-1.63 mg/mL).

RTHC-06287PreliminaryObservational

Identification of Three Novel Tetrahydrocannabinol Analogs in the European Market.

Dadiotis, Evangelos · 2025

Products marketed under invented cannabinoid names contained novel THC analogs that have never been found in cannabis plants and lack any toxicological data.

RTHC-06337PreliminaryObservational

Synthetic cannabinoids in Mayotte over a year in time and space: an example of high-frequency evolution of market.

Devault, Damien Alain · 2025

Thirteen different synthetic cannabinoid receptor agonists were identified across 195 samples (187 cigarettes, 8 powders).

RTHC-06352PreliminaryCase Report

Intranasal naloxone to treat suspected synthetic cannabinoid overdose: A case report and literature review.

Dickinson, Jaden · 2025

A 43-year-old man with schizoaffective disorder presented with altered mental status and respiratory depression after suspected K2 use.

RTHC-06408PreliminaryAnimal Study

Synthetic cannabinoid CUMYL-4CN-BINACA induces oxidative stress, ER stress, and apoptosis in brain and testicular tissues of male albino rats.

Eren Demir, Erdem · 2025

Subacute exposure produced dose-dependent increases in oxidative damage markers and decreases in antioxidant defenses across both organs.

RTHC-06870PreliminaryAnimal Study

Embryotoxicity Evaluation of Novel Synthetic Cannabinoid 4F-MDMB-BUTICA Using Zebrafish Embryos.

Kullebi, Berşan · 2025

LC50: 1.932 mg/L; EC50: 0.960 mg/L at 120 hours.

RTHC-07027PreliminaryAnimal Study

The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1α dysregulation and mitochondrial dysfunction.

Malheiro, Rui Filipe · 2025

Both synthetic cannabinoids enhanced neurite outgrowth at biologically relevant concentrations below 1 micromolar.

RTHC-07290PreliminaryAnimal Study

Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat.

Ozhan, Onural · 2025

Acute high-dose JWH-018 caused bradycardia and hypotension.

RTHC-07292PreliminaryCross-Sectional

Emerging Hemp-Derived Semi-Synthetic Cannabinoids, Absent Regulations: Patterns of Use and Adverse Effects Among a Sample of U.S. Cannabis Consumers.

Pabon, Elisa · 2025

Delta-8 THC (21.8%), THCP (24.4%), and Delta-10 THC (14.0%) were the most commonly used semi-synthetic cannabinoids.

RTHC-07302PreliminaryAnimal Study

Exacerbated cardiac dysfunction from combined alcohol binge and synthetic cannabinoid use.

Paloczi, Janos · 2025

Both alcohol and the synthetic cannabinoid CP55,940 independently caused dose-dependent declines in heart contractile function in mice.

RTHC-07408PreliminaryCase Report

Seven patients with analytically confirmed MDMB-4en-PINACA toxicity associated with the use of electronic vaping devices.

Pucci, Mark · 2025

Seven patients (median age 17, range 14-37) presented to UK hospitals after using vaping products contaminated with MDMB-4en-PINACA.

RTHC-07466PreliminaryCase Report

Long-Lasting Cognitive and Physical Impairment After Recreational Use of the Semisynthetic Cannabinoid Hexahydrocannabinonyl (HHC-C9): A Case Report.

Reiter, Nanna · 2025

After eating two cannabis cookies labeled as containing 40 mg "CC9" and biting a gummy with unknown contents, a man in his early forties required emergency admission for deficits in alertness and responsiveness.

RTHC-07635PreliminarySystematic Review

Synthetic Cannabinoid Withdrawal: A Systematic Review of Case Reports.

Sharma, Rishi · 2025

Most frequent withdrawal symptoms were psychosis (n=9, 82%), agitation/irritability (n=8, 73%), nausea/vomiting (n=6, 55%), seizures (n=5, 45%), tachycardia (n=4, 36%), and insomnia (n=3, 27%).

RTHC-07678PreliminaryObservational

Involuntary intoxication caused by vaping the synthetic cannabinoid ADB-BUTINACA: A case report.

Slob, Elise M A · 2025

Standard point-of-care drug tests were negative, but advanced LC-QTOF-MS analysis detected ADB-BUTINACA in the e-cigarette liquid.

RTHC-07846Preliminarypreclinical

Region-Specific Impact of Repeated Synthetic Cannabinoid Exposure and Withdrawal on Endocannabinoid Signaling, Gliosis, and Inflammatory Markers in the Prefrontal Cortex and Hippocampus.

Vadas, Evelin · 2025

WIN55,212-2 reduced IBA1 in prefrontal cortex (CB2-mediated).

RTHC-05158PreliminaryAnimal Study

Effects of Δ9-Tetrahydrocannabinol and the Aminoalkylindole K2/Spice Constituent JWH-073 on Cardiac Tissue and Mesenteric Vascular Reactivity.

Breivogel, Chris S · 2024

JWH-073 produced significantly greater maximal relaxation of mesenteric arteries (96% vs.

RTHC-05310Preliminaryanimal

CB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity.

Flavin, Audrey · 2024

Three CB1 NAMs (ABD1085, RTICBM189, PSNCBAM1) blocked JWH018 effects in cultured neurons.

RTHC-05442PreliminaryObservational

Identification and Health Risks of an Emerging Means of Drug Use in Correctional Facilities.

Kuai, David · 2024

All 18 patients had suspected strip exposure.

RTHC-05628PreliminaryAnimal Study

Timeframe Analysis of Novel Synthetic Cannabinoids Effects: A Study on Behavioral Response and Endogenous Cannabinoids Disruption.

Pineda Garcia, Jorge Carlos · 2024

All three synthetic cannabinoids (MDMB-CHMINACA, 5F-ADB-PINACA, APICA) caused locomotor disruption and sustained anxiety at all time points (1, 3, 5 hours).

RTHC-05746PreliminaryCase Report

Protonitazene detection in two cases of opioid toxicity following the use of tetrahydrocannabinol vape products in Australia.

Syrjanen, Rebekka · 2024

Two young males experienced opioid toxicity after using what they believed were THC vape products.

RTHC-05761PreliminaryAnimal Study

The impact of piperazine and antipsychotic co-exposures and CB1 blockade on the effects elicited by AMB-FUBINACA, a synthetic cannabinoid, in mice.

Thomsen, Lucy R · 2024

AMB-FUBINACA induced dose-dependent hypothermia and convulsions that were reversible with the CB1 antagonist rimonabant, confirming CB1 dependence.

RTHC-04365PreliminaryCase Report

From Euphoria to Emergency: Exploring the Role of K2/Spice in Diffuse Alveolar Hemorrhage.

Allena, Nishant · 2023

The patient presented with hemoptysis (coughing up blood) after smoking K2/Spice.

RTHC-04384PreliminaryCase Report

Abuse of Synthetic Cannabinoids and Cathinones in a Patient on Buprenorphine-Naloxone Treatment: A Case Report.

Awasthi, Harshal · 2023

The patient was unknowingly consuming synthetic cannabinoids and cathinones in a K2 blend while on buprenorphine/naloxone treatment.

RTHC-04417PreliminaryAnimal Study

Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.

Bilel, Sabrine · 2023

Repeated JWH-018 treatment (6 mg/kg daily for 7 days) induced psychomotor agitation, reduced social dominance and recognition memory, impaired prepulse inhibition, disrupted hippocampal long-term potentiation, decreased BDNF expression, and altered endocannabinoid system components in the striatum and hippocampus, all persisting 15+ days after last exposure..

RTHC-04430PreliminaryAnimal Study

Chronic exposure to a synthetic cannabinoid alters cerebral brain metabolism and causes long-lasting behavioral deficits in adult mice.

Bouter, Caroline · 2023

Treatment with WIN 55,212-2 (3 mg/kg) led to hypometabolism in the hippocampus, cerebellum, amygdala, and midbrain, persisting even after prolonged abstinence.

RTHC-04823PreliminaryAnimal Study

Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice.

Omran, Ghada A · 2023

WIN55,212-2 produced dose-dependent anxiogenic effects and reduced locomotor activity, with female mice less compromised than males.

RTHC-04847PreliminaryCase Report

Identification of 5F-Cumyl-PINACA, a Synthetic Cannabinoid, in the Herbal Material Used for Recreational Purposes in the Province of Trieste: Public Health Implications.

Peruch, Michela · 2023

The product tested negative for THC but positive for 5F-Cumyl-PINACA at a dose of 8.5 mg per package.

RTHC-03668PreliminaryAnimal Study

Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

Alzu'bi, Ayman · 2022

XLR-11 treatment caused upregulation of oxidative stress genes (NOX2, NOX4, iNOS), inflammatory markers (TNF-alpha, IL-1beta, IL-6), and pro-apoptotic gene Bax.

RTHC-03964PreliminaryCase Report

Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.

King, A · 2022

ADB-BUTINACA was found in 10 of 1,279 patients in the IONA study, all since February 2021, suggesting recent emergence.

RTHC-04090PreliminaryAnimal Study

Effects of synthetic (JWH-018) cannabinoids treatment on spermatogenesis and sperm function.

Mutluay, Duygu · 2022

JWH-018 (0.3 mg/kg for 9 days) caused significantly decreased sperm concentration, motility, and membrane integrity, reduced testosterone, increased abnormal sperm morphology, and seminiferous tubule degeneration.

RTHC-04269PreliminaryCase Report

Factor-guided diagnosis of coagulopathy associated with coumarin-contaminated synthetic cannabinoids.

Torian, Sterling C · 2022

A young adult presented with elevated INR without known medical history.

RTHC-04305PreliminaryAnimal Study

Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice.

Wilson, Catheryn D · 2022

Convulsant doses of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 did not produce seizure patterns on EEG despite causing visible convulsions.

RTHC-04317PreliminaryCase Report

A Case of Presumed Bonsai-induced Severe Toxic Optic Neuropathy.

Yasar, Erdogan · 2022

The patient presented with severely decreased vision in both eyes.

RTHC-03314PreliminaryCase Report

Synthetic cannabinoid induced ocular self-injury.

Malik, Kunal · 2021

Both patients had untreated schizophrenia and used K2 (synthetic cannabinoid).

RTHC-03395PreliminaryAnimal Study

Sex-dependent pharmacological profiles of the synthetic cannabinoid MMB-Fubinaca.

Oliveira da Cruz, José F · 2021

MMB-Fubinaca activated CB1 receptors with much greater potency than the standard cannabinoid agonist WIN55,512-2 in both mouse and human brain tissue.

RTHC-03590PreliminaryCase Report

Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?

Van Rafelghem, Babette · 2021

Following extensive vaping of 4F-MDMB-BINACA, the patient developed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, hepatocellular necrosis, and acute respiratory distress syndrome.

RTHC-02378PreliminaryAnimal Study

Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells.

Almada, Marta · 2020

All four cannabinoids decreased cell viability without membrane damage (indicating apoptosis, not necrosis).

RTHC-02398Preliminaryqualitative

Uses, Effects and Toxicity of Synthetic Cannabinoids from the Perspective of People with Lived Experiences.

Assi, Sulaf · 2020

Content analysis of 1,660 posts from 50 threads (2004-2016) revealed significant information exchange about SC consumption characteristics, modalities of use, experienced effects, and toxicity.

RTHC-02435PreliminaryAnimal Study

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.

Breivogel, Chris S · 2020

JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, methanandamide, or CBD.

RTHC-02475PreliminaryCross-Sectional

Personality Traits and Psychotic Proneness Among Chronic Synthetic Cannabinoid Users.

Cohen, Koby · 2020

SC users scored higher than natural cannabis users and non-users on neuroticism and schizotypal symptoms (SPQ-B), but lower on agreeableness and extraversion.

RTHC-02513PreliminaryAnimal Study

Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.

DeVuono, Marieka V · 2020

JWH-018 at 1 and 3 mg/kg produced conditioned gaping (nausea).

RTHC-02560PreliminaryAnimal Study

Synthetic cannabinoids enhanced ethanol-induced motor impairments through reduction of central glutamate neurotransmission.

Funada, Masahiko · 2020

Synthetic cannabinoids enhanced ethanol-induced motor impairment on a rotarod test.

RTHC-02565PreliminaryAnimal Study

In vitro and in vivo pharmacological evaluation of the synthetic cannabinoid receptor agonist EG-018.

Gamage, Thomas F · 2020

EG-018 had high affinity for CB1 (21 nM) and CB2 (7 nM) but behaved as a weak partial agonist, unlike typical synthetic cannabinoids.

RTHC-02885PreliminaryAnimal Study

The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice.

Trexler, Kristen R · 2020

AB-FUBINACA at 2+ mg/kg produced catalepsy, antinociception, hypothermia, and reduced locomotion, all blocked by CB1 antagonist rimonabant.

RTHC-02905PreliminaryAnimal Study

Different receptor mechanisms underlying phytocannabinoid- versus synthetic cannabinoid-induced tetrad effects: Opposite roles of CB1 /CB2 versus GPR55 receptors.

Wang, Xiao-Fei · 2020

CB1 deletion abolished tetrad effects for all three cannabinoids.

RTHC-01915PreliminaryCase Report

A case report positive for synthetic cannabinoids: are cardiovascular effects related to their protracted use?

Anzillotti, Luca · 2019

The report documents a cardiac tamponade case with toxicology positive for synthetic cannabinoids.

RTHC-01922PreliminaryCase Report

Synthetic Cannabinoid-Associated Multiple Organ Failure: Case Series and Literature Review.

Armstrong, Faith · 2019

All six patients had altered mental status and severe rhabdomyolysis (peak CK up to >320,000 U/L).

RTHC-01925PreliminaryCase Report

Delayed Intracerebral Hemorrhage after Synthetic Cannabis (Bonsai) Abuse; Case Report and Literature Review.

Aydin, Gülçin · 2019

The patient initially presented with dyspnea, hemoptysis, and agitation after synthetic cannabinoid ("Bonsai") use.

RTHC-01942PreliminaryAnimal Study

Pharmacological and Behavioral Effects of the Synthetic Cannabinoid AKB48 in Rats.

Bilel, Sabrine · 2019

AKB48 at low doses (0.25 mg/kg) preferentially stimulated dopamine release in the nucleus accumbens shell (reward center) and impaired visual reflexes at 0.3 mg/kg.

RTHC-01974PreliminaryCase Report

Disseminated Intravascular Coagulopathy Secondary to Unintentional Brodifacoum Poisoning via Synthetic Marijuana.

Chan, Abigail · 2019

The patient developed severe coagulopathy and cardiac arrest after synthetic cannabinoid use contaminated with brodifacoum.

RTHC-01990PreliminaryCross-Sectional

Cortical Thickness and Subcortical Volumes in Adolescent Synthetic Cannabinoid Users with or Without ADHD: a Preliminary Study.

Çolak, Çiğdem · 2019

SC users with and without ADHD had reduced cortical thickness in left caudal middle frontal and left superior frontal areas compared to controls.

RTHC-02086PreliminaryAnimal Study

Effects of the synthetic cannabinoid 5F-AMB on anxiety and recognition memory in mice.

Ito, Shiho · 2019

Central 5F-AMB produced anxiolytic effects and impaired recognition memory acquisition via CB1 receptors (blocked by AM251).

RTHC-02102PreliminaryAnimal Study

CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist.

Kevin, Richard C · 2019

CUMYL-4CN-BINACA acted as a potent CB1 receptor agonist and produced seizures at a lower dose than any previously tested synthetic cannabinoid.

RTHC-02138PreliminaryAnimal Study

Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory.

Li, Ren-Shi · 2019

JWH-018 elevated anandamide and 2-AG levels in the hippocampus by suppressing the enzymes that break them down (FAAH and MAGL).

RTHC-01733PreliminaryCross-Sectional

The effects of synthetic cannabinoids (SCs) on brain structure and function.

Livny, A · 2018

Fifteen chronic synthetic cannabinoid (SC) users and 15 healthy controls underwent MRI scans while performing cognitive tasks. SC users showed reduced total gray matter volume compared to controls, along with reduced volume in specific regions: middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex, and precuneus. On a working memory task (N-back), SC users performed worse behaviorally and showed diminished brain activation in the precuneus, cuneus, lingual gyrus, hippocampus, and cerebellum. On a response inhibition task (Go-No-Go), no group differences were found in either performance or brain activation. This was the first study showing both overall and region-specific gray matter volume reductions in chronic SC users, and the first to demonstrate impaired neural mechanisms for working memory specifically..

RTHC-01754PreliminaryCase Report

Impaired Driving Associated with the Synthetic Cannabinoid 5f-Adb.

McCain, K R · 2018

Law enforcement witnessed erratic driving by a 45-year-old male in fall 2017.

RTHC-01764PreliminaryCase Report

Acute myocardial infarction triggered by use of synthetic cannabis.

Mills, Brooke · 2018

A young woman presented to the hospital with an anterior ST elevation myocardial infarction (STEMI) shortly after using synthetic cannabis. ST elevation myocardial infarction is a serious type of heart attack involving complete blockage of a coronary artery. The temporal relationship between synthetic cannabis use and the cardiac event was notable, as the patient was young and otherwise not in a typical demographic for heart attacks. The case report highlighted the cardiovascular risks of synthetic cannabinoids, which are far more potent than natural cannabis and can cause coronary vasospasm, arrhythmias, and direct cardiac toxicity..

RTHC-01322PreliminaryAnimal Study

Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice.

Aguilar, María A · 2017

Mice pre-treated with the synthetic cannabinoid WIN 55212-2 during adolescence and then given chronic cocaine in adulthood showed a modified withdrawal profile compared to controls. Adolescent cannabinoid exposure prevented the anxiety increase normally seen during cocaine withdrawal.

RTHC-01349PreliminaryAnimal Study

Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. In vitro and in vivo studies.

Canazza, Isabella · 2017

In vitro testing revealed that all three synthetic cannabinoids (5F-ADBINACA, AB-FUBINACA, STS-135) had nanomolar affinity for both mouse and human CB1 and CB2 receptors, making them far more potent than THC.

RTHC-01373PreliminaryCross-Sectional

Psychometric Properties of the Turkish Versions of the Cannabis Use Problems Identification Test (CUPIT) and the Adult Cannabis Problems Questionnaire (CPQ).

Evren, Cuneyt · 2017

The CUPIT and CPQ questionnaires were validated in a Turkish clinical sample of 52 cannabis users and 45 synthetic cannabinoid users being treated for use disorders.

RTHC-01406PreliminaryAnimal Study

Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid 'Spice' compounds: comparison with Δ9 -tetrahydrocannabinol.

Hoffman, Alexander F · 2017

This study directly compared three widely abused synthetic cannabinoids from "Spice" products with THC in their ability to disrupt brain communication in the mouse hippocampus, a region critical for memory and learning. JWH-018 was the most potent, inhibiting synaptic transmission with an EC50 of approximately 15 nM, roughly 47 times more potent than THC (EC50 approximately 700 nM).

RTHC-01493PreliminaryAnimal Study

Antidote to cannabinoid intoxication: the CB1 receptor inverse agonist, AM251, reverses hypothermic effects of the CB1 receptor agonist, CB-13, in mice.

Pryce, Gareth · 2017

Researchers induced cannabinoid intoxication in mice using the synthetic CB1 agonist CB-13, which caused significant hypothermia and visible sedation.

RTHC-01512PreliminaryAnimal Study

Synthetic cannabinoids found in "spice" products alter body temperature and cardiovascular parameters in conscious male rats.

Schindler, Charles W · 2017

Researchers compared THC and four synthetic cannabinoids (CP55,940, JWH-018, AM2201, XLR-11) found in "Spice" products.

RTHC-01089PreliminaryCross-Sectional

Substance use is a risk factor for violent behavior in male patients with bipolar disorder.

Alnıak, İzgi · 2016

Researchers evaluated 100 male inpatients with bipolar disorder type I during mood episodes to identify factors associated with violent behavior (defined as physical aggression against others). Current substance use, rather than lifetime history of substance use disorder, was the key predictor: it was associated with a threefold increase in violence risk.

RTHC-01097PreliminaryAnimal Study

Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: Behavioral, electrophysiological and neurochemical evidence.

Barbieri, M · 2016

Researchers compared the cognitive effects of three synthetic cannabinoids (JWH-018, JWH-018-Cl, and JWH-018-Br) with THC in mice using a novel object recognition test. All three synthetic compounds dose-dependently impaired both short-term (2-hour) and long-term (24-hour) memory retention, and they were more potent than THC at producing these deficits. In hippocampal brain slice experiments, the synthetic compounds also disrupted electrically evoked synaptic transmission, long-term potentiation (LTP, a cellular mechanism of memory), and the release of both glutamate and GABA.

RTHC-01116PreliminaryCase Report

Unusual side effect of cannabis use: acute abdomen due to duodenal perforation.

Buyukbese Sarsu, Sevgi · 2016

This case report described a 16-year-old male who presented to the emergency department with abdominal distension, pain, and bilious vomiting.

RTHC-01118PreliminaryAnimal Study

Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on "tetrad", sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies.

Canazza, Isabella · 2016

Researchers conducted the first comprehensive pharmacological characterization of AKB48 and its fluorinated derivative 5F-AKB48, two synthetic cannabinoids sold as "Spice" products. Both compounds showed nanomolar affinity for CB1 and CB2 receptors in binding experiments.

RTHC-01137PreliminaryAnimal Study

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

De Luca, Maria Antonietta · 2016

Researchers characterized four third-generation synthetic cannabinoids (BB-22, 5F-PB-22, 5F-AKB-48, STS-135) and compared them to the earlier compound JWH-018. BB-22 and 5F-PB-22 had CB1 receptor binding affinities 30 and 26 times higher than JWH-018 respectively, with higher potency and efficacy as CB1 agonists.

RTHC-01185PreliminaryAnimal Study

[INCREMENT]9-Tetrahydrocannabinol discriminative stimulus effects of AM2201 and related aminoalkylindole analogs in rats.

Järbe, Torbjörn U C · 2016

AM2201 is a synthetic cannabinoid that has been found in "Spice" products sold as legal cannabis alternatives.

RTHC-01237PreliminaryAnimal Study

Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice.

Ossato, Andrea · 2016

Researchers tested JWH-250 and JWH-073, two synthetic cannabinoids frequently found together in "herbal blend" products, in mice.

RTHC-01305PreliminaryCross-Sectional

Do police arrestees substitute legal highs for other drugs?

Wilkins, Chris · 2016

Researchers interviewed 848 police detainees about their drug use, with a focus on whether legal highs (primarily synthetic cannabinoids) substituted for illegal drugs. Among legal high users, 96% had used synthetic cannabinoids (SC), and 94% of those reporting substitution had substituted natural cannabis.

RTHC-01306PreliminaryCross-Sectional

An exploratory study of the health harms and utilisation of health services of frequent legal high users under the interim regulated legal high market in central Auckland.

Wilkins, Chris · 2016

Researchers recruited 105 frequent legal high users from outside randomly selected licensed legal high stores in central Auckland during a period when synthetic cannabinoids were sold legally in New Zealand. Eighty percent used synthetic cannabinoids (SC), and use was intensive: 47% of SC users consumed daily or more.

RTHC-01004Preliminaryretrospective-cohort

Synthetic cannabinoid withdrawal: a new demand on detoxification services.

Macfarlane, Vicki · 2015

Researchers reviewed records from Auckland detoxification services over 12 months and found 47 people presenting for help with synthetic cannabinoid withdrawal.

RTHC-01028PreliminaryAnimal Study

JWH-018 impairs sensorimotor functions in mice.

Ossato, A · 2015

Researchers compared the synthetic cannabinoid JWH-018 (found in "Spice" and "herbal blends") with THC across a battery of sensorimotor tests in mice. JWH-018 impaired sensorimotor responses (visual, auditory, tactile) at extremely low doses (0.01-0.1 mg/kg), reduced spontaneous movement at intermediate doses, and caused convulsions, myoclonia, and hyperreflexia at high doses (6 mg/kg). THC at the same doses also reduced some sensorimotor responses but did not inhibit spontaneous locomotion and did not cause any neurological alterations like convulsions.

RTHC-00796PreliminaryAnimal Study

The hypocretin/orexin receptor-1 as a novel target to modulate cannabinoid reward.

Flores, África · 2014

Two complementary approaches pointed to the same result.

RTHC-00801PreliminaryCross-Sectional

Investigating correlates of synthetic marijuana and Salvia use in light and intermittent smokers and college students in a predominantly Hispanic sample.

Gutierrez, Kevin M · 2014

Across two studies at a U.S./Mexico border university and health clinic, researchers found that 9-10% of participants had ever used synthetic cannabinoids or Salvia divinorum.

RTHC-00882PreliminaryCase Report

A Gut Gone to Pot: A Case of Cannabinoid Hyperemesis Syndrome due to K2, a Synthetic Cannabinoid.

Ukaigwe, Anene · 2014

A 38-year-old man with a 10-year history of cannabis use and 1-year history of K2 (synthetic cannabinoid) use presented with episodic nausea, vomiting of clear fluids, and epigastric discomfort for one week.

RTHC-00684PreliminaryCase Report

Synthetic cannabinoid intoxication: a case series and review.

Harris, Carson R · 2013

Six patients presented to an emergency department over three months after using Spice products.

RTHC-00707PreliminaryCase Report

The synthetic cannabinoid withdrawal syndrome.

Nacca, Nicholas · 2013

Two patients presented with withdrawal symptoms from prolonged use of synthetic cannabinoids.

RTHC-00561PreliminaryAnimal Study

JWH-018 and JWH-073: Δ⁹-tetrahydrocannabinol-like discriminative stimulus effects in monkeys.

Ginsburg, Brett C · 2012

Researchers tested JWH-018 and JWH-073 (common synthetic cannabinoids in "Spice" and "K2" products) in monkeys trained to discriminate THC from placebo.

RTHC-00566PreliminaryReview

"Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans.

Gunderson, Erik W · 2012

The researchers conducted a systematic review of published reports on clinical effects of synthetic cannabinoids (SCs) in humans.

RTHC-00574PreliminaryAnimal Study

Apparent inverse relationship between cannabinoid agonist efficacy and tolerance/cross-tolerance produced by Δ⁹-tetrahydrocannabinol treatment in rhesus monkeys.

Hruba, Lenka · 2012

Rhesus monkeys trained to discriminate THC were given daily THC (1 mg/kg) for 3 or 14 days.

RTHC-00458PreliminaryReview

Spice drugs as a new trend: mode of action, identification and legislation.

Vardakou, I · 2010

The review examined the emerging problem of synthetic cannabinoids sold as "Spice" herbal products.

RTHC-00396PreliminaryCase Report

Withdrawal phenomena and dependence syndrome after the consumption of "spice gold".

Zimmermann, Ulrich S · 2009

A 20-year-old patient smoked Spice Gold daily for 8 months, developing classic signs of dependence: tolerance with dose escalation to 3 grams per day, continuous drug craving, continued use despite cognitive impairment, and neglect of professional duties. On hospital days 4-7 after cessation, he developed withdrawal symptoms: inner restlessness, drug craving, nightmares, profuse sweating, nausea, tremor, headache, elevated blood pressure (180/90 mmHg), and tachycardia (125 bpm). The patient reported experiencing a similar syndrome during a previous involuntary abstinence period, which resolved when he resumed use. Urinary drug screens were negative, as standard tests did not detect synthetic cannabinoids.

RTHC-07835lowclinical-observation

Synthetic Cannabinoid (Mojo)-Induced ST-Segment Elevation Myocardial Infarction: A Case Report.

Udoh, Kubiat E · 2025

A 32-year-old with ASCVD risk 3.6% presented with chest pain 4 hours after smoking Mojo.

RTHC-05077lowanimal study

Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice.

Alzu'bi, Ayman · 2024

AB-FUBINACA caused significant recognition memory impairment along with hippocampal histopathological changes.

RTHC-05123lowcross-sectional survey

Synthetic Marijuana: Assessment of Usage, Motivation and Associated Risks in Adolescent Substance Users.

Baweja, Raman · 2024

Of 80 adolescents, 49% used natural marijuana only and 51% used both synthetic and natural.

RTHC-04943very-lowCase Report

Fatal Overdose with the Cannabinoid Receptor Agonists MDMB-4en-PINACA and 4F-ABUTINACA: A Case Report and Review of the Literature.

Simon, Gábor · 2023

Forensic analysis confirmed the presence of both MDMB-4en-PINACA and 4F-ABUTINACA in the deceased, with autopsy revealing acute myocardial ischemia and pulmonary edema consistent with synthetic cannabinoid toxicity..