Evidence briefing

Psychiatric presentations after novel psychoactive substances including synthetic cannabinoids and cathinones

Written by a language model from the cited research, from 5 full texts and the abstracts of the other 7. No human author wrote or checked this text. Not peer reviewed.

Generated 21 August 2026 · 12 sources cited, 2015–2026 · Full text read for 5 of 12 sources · Not peer reviewed

Subjectsynthetic substances in psychiatry

QuestionWhat psychiatric and psychopathological consequences have been described in people using novel psychoactive substances, and how do presentations after synthetic cannabinoids or cathinones compare with those after classical cannabis or amphetamines?

AnswerReviews of case material and small observational studies have associated novel psychoactive substances with psychosis, agitation, self-harm and medical complications that may be more severe or phenotypically unusual than those of cannabis or methamphetamine. Synthetic cannabinoids have been linked in systematic syntheses to visual hallucinations, agitation and, in some reports, a more lasting psychotic course. Synthetic cathinones have shown psychiatric severity comparable to methamphetamine in one Taiwanese emergency comparison, with higher odds of physical complications there. Many compounds are thought to act on cannabinoid, monoamine and serotonergic systems, yet pharmacokinetics and pharmacodynamics remain incompletely characterised. The evidence base is largely case series, toxicovigilance and systematic reviews of uncontrolled reports, often with polysubstance confounding and incomplete laboratory confirmation. No randomised trials of psychiatric management were identified, so inferences stay modest and class-specific extrapolation is uncertain.

Keywords novel psychoactive substances; synthetic cannabinoids; synthetic cathinones; drug-induced psychosis; psychiatric emergency; suicidality

What the evidence shows

Every figure in this review was checked against the material read for the cited sources — their abstracts, and the open-access full text where one was retrieved. ‡ marks one found only in a source other than the one cited. See Limitations.

A 2015 narrative review for psychiatrists listed classes of novel psychoactive substances and suggested that they act on dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate and kappa-opioid receptors. Users were described as typically attracted by intense psychoactive effects and likely lack of detection in routine screens.¹
Using dedicated web-crawling software called NPS.Finder, a 2019 review preliminarily identified a few thousand novel psychoactive substances, about four-fold higher than agency tallies. That work linked synthetic cannabinoids, new synthetic opioids, ketamine-like dissociatives, novel stimulants and novel psychedelics to psychopathological consequences.²
Focusing on synthetic cannabinoids and cathinones, a mini-review concluded that NPS-induced psychoses appear extremely different from classical presentations and tabulated desired versus adverse effects by pharmacological class.³
Paranoid ideation, brief psychotic episodes and a persistent picture designated Spiceophrenia were listed among reported untoward effects of synthetic cannabinoids, while synthetic cathinones were placed on a spectrum from mild agitation to severe psychosis.³
Raised central dopamine for psychedelic phenethylamines, synthetic cathinones and stimulants, 5-HT receptor subtype activation, and NMDA antagonism among phencyclidine-like dissociatives were linked in a 2023 narrative update on stimulant and hallucinogenic novel psychoactive substances.⁴
Designer-drug mechanisms were surveyed in a 2020 toxicology review, which concluded that stimulants such as amphetamines and cathinones primarily interact with monoamine transporters. Synthetic cannabinoids acting at the CB1 receptor were judged to have a less desirable effect profile and more severe adverse effects compared with cannabis.⁵
Relative serotonergic versus dopaminergic activity, indexed by the dopamine/serotonin transporter inhibition ratio in vitro, may help predict psychotropic effects, toxicity and addiction potential, according to a 2015 overview of novel psychoactive substances as modulators of monoamine signalling.⁶
Epidemiological work among 85 studies from 2005 through 2022 consistently suggested higher psychosis risk with novel psychoactive substances than with traditional substances (odds ratios 4.4^‡-5.2 for synthetic cannabinoids versus cannabis, as summarised therein). Distinctive synthetic-cannabinoid pictures in that synthesis included visual hallucinations (73-84%), agitation (79-91%) and anxiety (62-76%).⁷
From 4477 identified studies, 95 papers were retained and found synthetic cannabinoids to be the class most frequently implicated in acute psychosis and, in some reports, in persistent or relapsing psychotic disorders. Schneiderian first-rank symptoms in some cases were taken to indicate phenomenological overlap with schizophrenia and a possible risk of transition.⁸
Follow-up lasting at least six months was present in 28 of 58 studies, 22 of which were rated high quality, in a synthesis focused primarily on synthetic cannabinoids, synthetic cathinones and NBOMe hallucinogens. The authors suggested enhanced psychiatric risk with prolonged sequelae, but the synthesis was narrative and drew heavily on uncontrolled follow-up.⁹
In one comparative cohort summarised therein, hospitalisations for synthetic cannabinoid-related psychosis lasted 43.45 days versus 22.91 days for cannabis-related psychosis. A case series summarised there found prolonged psychotic episodes beyond five months in approximately 30% of patients.⁹
Synthetic cathinone-related rhabdomyolysis rates reached 63% in an outbreak series summarised therein, and NBOMe exposures were associated with fatality rates of approximately 15% and Intensive Care admission rates of approximately 40%.⁹
In a matched case-control study from a Taiwanese psychiatric emergency department, 24 patients^‡ with synthetic cathinone intoxication were compared with 48 patients with methamphetamine intoxication after immunoassay and liquid chromatography–quadrupole time-of-flight mass spectrometry of urine. The two groups had similar psychotic-symptom severity and rates of violence and self-harm, but higher odds of physical complications in the cathinone group (odds ratio 8.55, 95% confidence interval 2.15-34.03). Family histories of substance use and criminal records were less prevalent among those with cathinone intoxication.¹⁰
Physical complications, defined there as rhabdomyolysis, acute kidney failure, dystonia or muscle weakness, occurred in 11 of 24 cathinone cases versus 4 of 48 methamphetamine cases. Mean Brief Psychiatric Rating Scale totals were 71.7 versus 67.3.¹⁰
Sixteen articles assembled up to March 2021 reported that suicidality and self-injurious behaviour appeared frequently associated with cathinones, synthetic cannabinoids and new synthetic opioids. Eligible material included single-patient intoxications and retrospective series rather than controlled cohorts.¹¹
Four acute psychiatric inpatients with psychosis and confirmed synthetic cannabinoid receptor agonist use were described with Positive and Negative Syndrome Scale ratings, vital-sign monitoring with the National Early Warning Score, and individualised plans using benzodiazepines and antipsychotics. Urine and oral-fluid assays were used alongside routine screens, and observation levels and leave status were recorded.¹²

What remains open

Temporality and causality between novel psychoactive substance exposure and persistent psychotic disorder have not been established in longitudinal controlled designs.
It remains unclear whether use raises psychosis risk or whether people already prone to psychosis are more likely to use these substances.
Rapid turnover of chemical structures means that published clinical series lag behind substances actually in circulation.
Most studies cannot exclude confounding by concurrent classical drugs or pre-existing psychiatric vulnerability.
Whether presentations after synthetic cannabinoids differ in kind from cannabis-induced psychosis, or only in typical severity, is still disputed across reviews.
Randomised evaluations of pharmacological or psychosocial management for novel psychoactive substance-related psychosis have not been reported.

Methods

Search strategy. Candidate records were retrieved on 21 August 2026 from OpenAlex and Europe PMC, using the search strings ‘novel psychoactive substances psychiatry’; ‘synthetic cannabinoids psychiatric effects’; ‘synthetic cathinones psychosis’; ‘NPS-induced psychiatric disorders’. Records without a retrievable abstract were discarded, leaving 40 for screening. Each remaining record was assessed for how directly it addresses synthetic substances in psychiatry and labelled direct, related or background; 12 were cited here and are listed in Table 1.

Evidence handling. Titles and abstracts were read for every record, and the open-access full texts of 5 sources were retrieved from their open-access copies and read alongside them (marked in Table 1); claims resting on the remaining sources draw on no data beyond an abstract. Decimals, percentages, effect estimates and quantities carrying a clinical unit were then checked automatically, each against the sources its own sentence cites, within exactly the material shown to the model — the abstracts plus those full-text excerpts. A figure that could not be located, or that appears only in a source other than the one cited, is flagged under Limitations.

Generation. Search planning, source curation and drafting were performed by a large language model (x-ai/grok-4.6). Source retrieval, relevance tabulation, citation numbering, Table 1, Fig. 1 and the statistical check are deterministic and were not model-generated.

Evidence assessment

Of the 12 sources cited, 10 address the review question directly, 2 are related and 0 provide background only; they were published in 2015–2026. The composition of the evidence base is shown in Fig. 1.

Limitations. This synthesis was prepared from the open-access full texts of 5 cited sources and the abstracts of the remaining 7. Where only an abstract was available, effect estimates, methodological detail, and the limitations that authors report only in a full text were unavailable, so the strength of those studies could not be appraised here. 3 numerical values reported above (4.4, -5.2, 24 patients), each marked ‡ where it appears, are found in cited sources other than the ones their sentences credit. The figures are present in the evidence base, but the attributions do not hold and should be checked before they are quoted. The text below should therefore be read as a working draft rather than a finished review.

Table 1 | Characteristics of the cited evidence. Design is inferred from each record's title, journal and index metadata and is left blank where it could not be inferred; no quality appraisal was performed. Relevance is the curation label for how directly each source addresses the review question. Read records whether the model saw the source's open-access full text or its abstract only.

Ref.	Study	Year	Source	Design	Relevance	Read
1	Schifano et al.	2015	World Psychiatry	—	Direct	Abstract
2	Schifano et al.	2019	Psychological Medicine	—	Direct	Abstract
3	Orsolini et al.	2019	Frontiers in Psychiatry	—	Direct	Full text
4	Schifano et al.	2023	Expert Review of Clinical Pharmacology	—	Direct	Full text
5	Luethi & Liechti	2020	Archives of Toxicology	—	Related	Abstract
6	Liechti	2015	Swiss Medical Weekly	—	Related	Abstract
7	Ricci et al.	2025	Neuroscience and biobehavioral reviews	Reviews	Direct	Abstract
8	Mosca et al.	2025	Neuroscience and biobehavioral reviews	Reviews	Direct	Abstract
9	Ricci et al.	2026	Psychiatry research	Reviews	Direct	Abstract
10	Lin et al.	2023	Journal of Clinical Psychopharmacology	—	Direct	Full text
11	Chiappini et al.	2021	Medicina	Reviews	Direct	Full text
12	Bonaccorso et al.	2018	Brain Sciences	Observational	Direct	Full text

Glossary

novel psychoactive substances: Psychoactive compounds newly available on the recreational market, often not yet under international control.
synthetic cannabinoids: Laboratory-made compounds that agonise cannabinoid receptors and are often sold as herbal smoking mixtures.
synthetic cathinones: Synthetic analogues of the khat alkaloid cathinone that act as stimulants via monoamine transporters.

References

Schifano, F. et al. Novel psychoactive substances of interest for psychiatry. World Psychiatry (2015). Cited by 324
Schifano, F. et al. New/emerging psychoactive substances and associated psychopathological consequences. Psychological Medicine (2019). Cited by 120
Orsolini, L. et al. The Bridge Between Classical and “Synthetic”/Chemical Psychoses: Towards a Clinical, Psychopathological, and Therapeutic Perspective. Frontiers in Psychiatry (2019). Cited by 42
Schifano, F. et al. Stimulant and hallucinogenic novel psychoactive substances; an update. Expert Review of Clinical Pharmacology (2023). Cited by 35
Luethi, D. & Liechti, M. E. Designer drugs: mechanism of action and adverse effects. Archives of Toxicology (2020). Cited by 263
Liechti, M. E. Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalling. Swiss Medical Weekly (2015). Cited by 189
Ricci, V. et al. Novel psychoactive substances and psychosis: A comprehensive systematic review of epidemiology, clinical features, neurobiology, and treatment. Neuroscience and biobehavioral reviews (2025). Cited by 1
Mosca, A. et al. Novel psychoactive substances (NPS) as a risk factor for psychosis: A systematic review of the literature. Neuroscience and biobehavioral reviews (2025). Cited by 1
Ricci, V. et al. Acute and long-term psychiatric consequences of synthetic cannabinoids and related novel psychoactive substances: A systematic review. Psychiatry research (2026).
Lin, C., Chen, J. & Chan, C. Comparison of Psychiatric and Clinical Profiles Between People Who Use Synthetic Cathinones and Methamphetamine. Journal of Clinical Psychopharmacology (2023). Cited by 8
Chiappini, S. et al. New Psychoactive Substances and Suicidality: A Systematic Review of the Current Literature. Medicina (2021). Cited by 68
Bonaccorso, S. et al. Synthetic Cannabinoid use in a Case Series of Patients with Psychosis Presenting to Acute Psychiatric Settings: Clinical Presentation and Management Issues. Brain Sciences (2018). Cited by 47

Additional information

Data availability. No new data were generated. All evidence cited is published and openly indexed; 12 of the 12 cited records resolve through the links in the reference list.

Author contributions. Search planning, source curation and drafting were carried out by an automated pipeline (articlegen, x-ai/grok-4.6). No human author wrote or verified the text before publication of this draft.

Competing interests. None declared.

Peer review. This article has not been peer reviewed and is not a publication of record.