Substances led to Psychosis: A Systematic Review
SYSTEMATIC REVIEW

Substances led to Psychosis: A Systematic Review

The Open Psychology Journal 30 May 2024 SYSTEMATIC REVIEW DOI: 10.2174/0118743501297735240510161825

Abstract

Background

Psychosis is one of the mind-related disorders that has been common in the new generation, and it has an increasing trend. Psychosis is a variable feature of mood that could be a result of substance use, which includes a few psychiatric and neurologic symptoms. Common symptoms of psychoses are delusions, hallucinations, disorganized thinking, grossly disorganized, or abnormal motor behavior. An array of illicit substances and drugs that can lead to psychosis include cannabinoids, cocaine, amphetamines, methamphetamines, alcohol, etc.

Objectives

The main aim of this review was to discover, analyze, and combine the information concerning substances that could potentially cause psychoses.

Methods

We conducted a literature search on the following network databases: PubMed, Scholar, Science Direct, PubChem, Scopus, and Web-Of-Science. We selected 14 studies potentially relevant articles published from 1990 to 2023 for detailed evaluation. The systematic review was done adhering to PRISMA guidelines. We gathered the important primary studies of eligible systematic reviews and collected data on the interventions employed in these studies to comprehend the strategies that were pursued.

Results

Our result indicated that there are a few substances, which include Cannabinoids, Alcohol, Amphetamine, Cocaine, Nicotine, Kratom, Cathinone, etc., that may lead to psychoses with average to high possibility.

Conclusion

Evidence regarding frequently encountered substances that might contribute to psychosis presents an opportunity to develop customized interventions in the form of user-friendly menus aimed at meeting individuals' requirements and urging them to refrain from consumption.

Keywords: Psychosis, Illicit drugs, Youth, Antibiotics, Neurologic symptoms, Alcohol.

1. INTRODUCTION

Experimental data indicate diverse subgroups of individuals diagnosed with various severe psychiatric disorders, such as new-onset psychosis and substance-induced psychosis, frequently exhibit abnormalities. These abnormalities commonly manifest in clinical practice [1]. Psychosis is one of the mind-related disorders that has been common in the new generation, and it has an increasing process [2]. Psychosis is an inconstant feature of mood that could be an outcome of substance use, which includes a few functionally psychiatric and neurologic symptoms. In the initial version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), psychosis was described as ” abnormalities in one or more of the following five domains: delusions, hallucinations, dis- organized thinking speech, grossly disorganized or abnormal motor behavior, and negative symptoms” or “gross impairment in reality testing” that interferes with the capacity to meet the ordinary demands of life [3] (Fig. 1). There are a few kinds of substances and drugs that can lead to psychosis; however, the reasons for this association. A clear connection between drug use and the appearance of psychotic symptoms has received considerable backing. Some studies indicate that drugs like cannabinoids, cocaine, amphetamines, methamphe- tamines, alcohol, methylphenidates, nicotine, Kratom, hallucinogens, and certain antibiotics possess psycho- tomimetic properties. [4]. Also, drug abuse has been one of the most popular behaviors in the new generation, and the chemical formula of psychoactive drugs is progressing. Thus, it is probable that substance-induced psychosis may become a pandemic in the future [5]. This review aimed to find, analyze, and summarize the information on substances that could cause psychoses. In other words, it may cause temporary psychotic symptoms as a result of immediate intoxication and psychotic disorders [5, 6]. In another hand, it has been strengthened by teenagers [7-11]. The research gaps of recent articles are limited focus on specific substances, Insufficient research on longitudinal effects, variability in study methodologies, lack of research on specific populations, limited exploration of underlying mechanisms, and Sparse data on effective interventions. Therefore, these potential research gaps could provide avenues for future research to deepen our understanding of the relationship between substances and psychosis; the aim of this article is to resolve these research gaps.

Fig. (1). The DSM-5, the Diagnostic and Statistical Manual of Mental Disorders fifth edition, the criteria for substance-induced psychosis.
Table 1.
Data extraction.
Authors Year Title Focus Sample Main Results
Fiorentini, Alessio; Sara Volonteri, Lucia; Dragogna, Filippo; Rovera, Chiara; Maffini, Michele; Carlo Mauri, Massimo; A. Altamura, Carlo [1]* 2011 Substance-Induced Psychoses: A Critical Review of the Literature Drugs that may lead to psychoses 23 Most of the drugs, such as cannabinoids, may lead to psychoses.
Dharav Shah,
Prabhat Chand,
Mrunal Bandawar,
Vivek Benegal,
Pratima Murthy [75]*
2017 Cannabis-induced psychosis and subsequent psychiatric disorders Cannabis and psychoses 38 Cannabis may lead to psychoses.
Vera L. Alves,João L. Gonçalves,Joselin AguiarCQM – Centro de Química da Madeira, Universidade da Madeira, Funchal, Portugal;,Helena M. Teixeira &José S. Câmara [74]* 2020 The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review Synthetic cannabinoids and psychiatric disorders 42 Synthetic cannabinoids can considerably lead to psychoses.
Anna Sunshine, Jon McClellan [3]* 2023 Practitioner Review: Psychosis in children and adolescents Psychoses in children 58 Drug use by children can lead to psychosis.
F. Schifano,
F. Napoletano,
S. Chiappini,
A. Guirguis,
J. M. Corkery,
S. Bonaccorso,
A. Ricciardi,
N. Scherbaum
And A. Vento [4]*
2019 New/emerging psychoactive substances and associated psychopathological consequences New drugs and psychiatric disorders. 66 Future drugs lead to psychotic symptoms.
Hannah E. Brown, Yoshio Kaneko & Abigail L. Donovan [6]* 2019 Substance-Induced Psychosis and Co-occurring Psychotic Disorders Psychosis because of drug use such as cocaine, etc. 87 Amphetamine and cocaine considerably can lead to psychoses.
NEUFELD, NICHOLAS H. MD; MOHAMED, NOURHAN S. MD; GRUJICH, NIKOLA MD; SHULMAN, KENNETH MD [45]* 2017 Acute Neuropsychiatric Symptoms Associated with Antibiotic Treatment of Helicobacter Pylori Infections: A Review Antibiotics as a risk factor for psychiatric patients. 91 Antibiotics may lead to psychoses.
Pedro Gurillo, MD,
Dr. Sameer Jauhar
MRCPsych,
Robin M Murray
FRS, James H MacCabe, FRCPsych [9]*
2015 Does tobacco use cause psychosis? Systematic review and meta-analysis Smoking and psychosis 94 Nicotine may be a factor that increases the incur of psychosis
M.C. Cancino Botello,
M.D.L.A. Canseco Navarro,
A. Peña Serrano,
F. Molina López
and
J.M. Hernández Sánchez [38]*
2020 Psychosis, cause or consequence of substance use disorder Drug use and psychotic symptoms 102 Drugs lead to psychotic symptoms considerably.
M.C. Mauri a, C. Di Pace a, A. Reggiori a, S. Paletta a, A. Colasanti [12]* 2017 Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up Substance abuse and psychiatric disorders. 108 Substance abuse lead to psychotic symptoms.
Corinne Cather, Gladys N. Pachas, Kristina M. Cieslak & A. Eden Evins [21]* 2017 Achieving Smoking Cessation in Individuals with Schizophrenia: Special Considerations Smoking as a risk factor for psychotic patients. 157 Smoking may lead to psychoses in a long-term use.
L. R. Valmaggia
, F. L. Day, C. Jones
, S. Bissoli, C. Pugh
, D. Hall, S. Bhattacharyya
, O. Howes, J. Stone
, P. Fusar-Poli, M. Byrne
And P. K. McGuire [76]*
2014 Cannabis use and transition to psychosis in people at ultra-high risk Cannabinoids and psychoses 198 Cannabinoids may strongly lead to psychoses.
Khadija Pasha, Salomi Paul, Muhammad S. Abbas, Sondos T. Nassar, Tasniem Tasha, Anjali Desai
, Anjana Bajgain, Asna Ali, Chandrani Dutta, Abeer O. Elshaikh [23]*
2023 Psychosis Induced by Methylphenidate in
Children and Young Patients with AttentionDeficit Hyperactivity Disorder
Methylphenidate and psychosis 202 Methylphenidate leads to psychotic symptoms.
G. Martinotti1
, M. Di Nicola2
, D. Quattrone1
, R. Santacroce1
, F. Schifano, R. Murray4
, M. Di Giannantonio1 [64]*
2015 Novel psychoactive substances and induced phenomena in psychopathology:
the lysergic psychoma
psychotic symptoms by drug use 212 Methamphetamine, Amphetamine, methylphenidates, etc., can lead to psychoses.

2. MATERIALS AND METHODS

The databases include PubMed, Scholar, Science Direct, PubChem, Scopus, and Web-Of-Science. The steps involved in conducting this systematic review are

1-Formulating the research question (Clearly defining the research question “Which substances may lead to psychoses?” or hypothesis “Most of the usual drugs and some Antibiotics may lead to psychoses.” that the systematic review aims to address)

2-Developing inclusion and exclusion criteria (Setting specific criteria for including or excluding studies based on relevance and quality. The inclusion criteria include all clinical studies concerning adult (more than 17 years old) patients, published in English, content directly relevant to substance-induced-psychosis, report original patient, and studies defining drugs that can be related to psychosis.Exclusion criteria include studies with less than 10 participants, case reports, animal studies, articles that were not available in English, content related to other disorders like schizophrenia, not concerned with the field of substance-induced-psychosis, repeated research, unavailable full research (Tables 1 and 2), 3-Systematic search for studies (Conducting a comprehensive and systematic search across multiple databases such as PubMed, Scholar, and Science Direct, PubChem, Scopus, and Web-Of-Science to identify all relevant studies), 4-Screening and selecting studies (Reviewing titles, abstracts, and full texts of potentially relevant studies to determine which ones meet the inclusion criteria. We focused on review articles for our results. If the database did not have that filter, we looked for search terms related to reviews (like Review, systematic review, and meta-analysis) in our search strategy. Our main search topics were 'substance use and psychosis' and 'psychological intervention' (including psychological symptoms and behavior therapy, for instance) (Fig. 2). 5-Data extraction (Extracting relevant data from each included study using a predefined data extraction form), 6-Quality assessment (Assessing the quality of included studies to evaluate their risk of bias and methodological rigor), 7-Data synthesis (Analyzing and synthesizing the findings of the included studies using narrative synthesis which involves summarizing and qualitatively analyzing the findings of individual studies to identify patterns, themes, and discrepancies and qualitative thematic analysis methods to identify and interpret recurring themes, patterns, or discrepancies across the included studies. This can enrich the understanding of complex phenomena), 8-Interpreting results (Drawing conclusions based on the synthesized evidence and discussing implications).

3. RESULTS

3.1. Eligible Reviews

The search of the databases has returned 213 references. After excluding 116 duplicates based on title, we screened the titles of 97 studies. After excluding 79 duplicates based on abstract, we screened abstracts of 18 studies. We managed to obtain 14 complete texts. Fig. (1) summarizes the screening process described above. The reviews that were included had differences, as outlined below. Our research has found 14 studies examining the relationship between substance use and psychosis. Although the methodologies of studies and substance use psychosis criteria have varied, there was a considerable consistency between substance use and psychosis.

3.2. Conceptualization of Substance-induced Psychosis (SIP) in the Eligible Reviews

The current research findings have provided insight into the intricate connection between psychotic symptoms and the utilization and misuse of illegal substances. Moreover, there are instances where chronological factors alone are inadequate to establish a clear cause-and-effect connection between the substances and psychosis. To determine if psychotic symptoms in individuals with a history of drug use are truly independent of the drugs, these symptoms must persist even after a prolonged period of abstaining from psychoactive substances. It's worth noting that drug-induced psychosis is generally expected to resolve during a period of abstinence. People with drug-induced psychosis, in contrast, had a higher tendency to abuse multiple drugs and appeared to experience prolonged hallucinations even after stopping drug use [12].

Table 2.
Inclusion and exclusion criteria refer to the requirements for being included or excluded from a particular group or study.
Inclusion Criteria Exclusion Criteria
• All clinical studies concerning adult (more than 17 years old) patients
• Published in English
• Content directly relevant to substance-induced-psychosis
• Report original patient
• Studies defining drugs that can be related to psychosis
• Studies with less than 10 participants
• Case reports
• Animal studies
• Articles which were not available in English
• Content related to other disorders like schizophrenia, not concerned with the field of substance-induced-psychosis
• Repeated researches
• Unavailable full researches

3.3. Cannabinoids

In 2019, cannabinoids were the most commonly used illegal substance, with 22.2 million adults in Europe having used cannabis [13]. The point is that the effect of cannabis is related to its tetrahydrocannabinol (THC) content. THC causes negative effects associated with cannabis, such as cognitive impairments and the promotion of psychosis and anxiety [14]. This receptor is mainly found on peripheral nerve terminals. Cannabidiol (CBD) appears to be the second most prevalent cannabinoid that does not seem to cause any signs of psychosis. Marijuana includes 20% THC, and its concentrates include hash oil, wax, and edibles containing 60% THC [15-18] (Table 3).

3.4. Alcohol

Alcohol has a main role in substance use disorder, and alcohol-use disorders are associated with a considerable burden in terms of morbidity and mortality [19]. Psychotic symptoms can occur in several clinical conditions that are related to alcohol use and can lead to first-episode psychosis as well ref. Despite the main role of alcohol in substance use disorders, recent studies on substance-induced psychotic disorders have generally shown psychoses are usually induced by illicit drug use. Alcohol-induced psychotic disorder is a severe mental disorder with poor outcome [20]. However, the point is that it can be cured by behavior therapy with considerable outcomes (Table 3).

Fig. (2). PRISMA 2020 flow chart.

3.5. Nicotine

Nicotine is one of the most popular substances that has been used by a large group of people, especially young generations. It is the basic substance used to make cigarettes, and it comes from tobacco, which is a plant. Usually, people smoke cigarettes during adolescence, so there can be a huge misuse by individuals, and it has been associated with an increased risk factor of psychosis REF. Also, genetics may influence this association as genes associated with psychosis have been shown to overlap with those for cigarette smoking ref. It also increases cytochrome CYP1A2 enzyme activity, so it increases metabolism in a way [21]. Behavioral therapy can be useful even more than medicine in quitting smoking (Table 3).

Table 3.
The main features of the canonical of substances led to psychosis.
Substance Antidote Exposure Treatment Symptoms Neurotransmitter/pathways/receptors Implicated Chemical Structure
Cannabinol Naloxone (97) Oral, inhaled. (35) Decreasing THC levels in cannabis leads to decreasing the risk factor of psychotic disorder even for daily users(34) Reducing the level of THC in cannabis lowers the likelihood of developing a psychotic disorder, even for individuals who use it daily.
(36)
They influence the endocannabinoid system, specifically by fully activating CB1 and CB2 receptors.

C21H26O2
Alcohol Metadoxine, Fomepizole Drink(self-use and used by moms) Behavioral therapy Visual illusion, nauseous, loss of regular movements -

C2H6O
Nicotine Benzodiazepines, Atropine, Ventilator, Intravenous fluids Inhalation, insufflation, oral,
rectal.
Medical care, behavioral therapy - -

C10H14N2
Amphetamine (psychostimulant) Benzodiazepines (98) Oral (self-used by youth) Medical care and do not misuse Serotoninergic syndrome, Psychosis, Paranoid ideation, Impulsivity, Mania, Agitation, Mood disorders like serotonin syndrome (Serotoninergic syndrome), psychosis, paranoid thoughts, impulsive behavior, manic episodes, and agitation are commonly associated with the use of psychostimulants.
These drugs traditionally focus on activating the monoaminergic systems, resulting in higher levels of serotonin (5-HT), dopamine (DA), and/or norepinephrine (NA) C9H13N Cocaine (psychostimulant) Benzodiaze pines in the brain.


C9H13N
Cocaine (psychostimulant) Benzodiazepines (98) Oral, inhaled (used by mouth mostly) Do not misuse medical care 90% of the participants exhibited paranoid delusions, while 96% reported experiencing hallucinations, paranoia, and suspicious beliefs. Psychostimulants, in the traditional sense, mainly focus on the monoaminergic systems, resulting in elevated levels of SER, DA, and/or NA in the extracellular space.

C17H21NO4
Kratom Naloxone commonly used by chewing, as a tea, powdered in capsules and pills, or extracted for use in liquids Medical care - -

C23H30N2O4
Hallucinogens (Tryptamines) Naloxone Inhalation,
Intravenous,
Oral
The main chemical is in a kind of mushroom, so do not misuse Perception will be interrupted, and alteration in the perception, spontaneous reoccurrence of perceptual disturbance, and the illusion of movement will exist. All three subgroups share a common mechanism in the serotonergic system, represented by the agonism/partial agonism at the 5-HT2A receptor (activation), 5-HT1A, and 5-HT2C. However, Various hallucinogenic/psychedelic substances might have distinct interactions with various neurotransmitters, such as NMDA receptors, σ-receptors, μ-opioid receptors, and muscarinic receptors, in addition to their ability to inhibit serotonin and dopamine reuptake at their respective transporters.

C10H12N2
Phencyclidine Diazepam,
haloperidol, chlorpromazine
Smoking,
by mouth,
snort, injection.
Medical care PCP exhibits more intense psychotic effects, such as hallucination and delusion, especially illogical thinking (79).
Apathy (lack of interest), decreased talking, repetitive speech, and catatonic posturing (unusual body movements).
-

C17H25N
Entactogens, (MDMA) Medical care delusions (96%), hallucinations (96%), disorganization (96%). Feeling down (90%) with reduced emotional expression (81%),
(77).
- - -

C11H15NO2
Antibiotics Use them in a limited amount. - - - - -
Note: MDMA: 3,4-Methyl enedioxy methamphetamine, commonly known as ecstasy.

3.6. Amphetamine

Amphetamine is a strong central nervous system stimulant. Amphetamines, such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), belong to a class of compounds called phenethylamines that induce catecholaminergic effects in the CNS and peripheral circulation. Nowadays, amphetamines are clinically used to treat short-term obesity, narcolepsy, and attention deficit disorder with hyperactivity [22]. Due to recent studies, psychosis following amphetamine use is characterized by delusions, visual hallucinations, and symptoms resembling acute psychosis most commonly observed in schizophrenia. There is an obvious pattern of high dosage and daily usage correlating with higher risks of substance-induced psychosis. Amphetamines impair the cognitive thought process and precede acute psychosis. This shows that continued impairment due to amphetamine use is a precursor to psychosis. (Table 3) [23, 24].

3.7. Cocaine

Cocaine is one of the most common substances that leads to transitory paranoia [25]. Cocaine is widely recognized to be associated with several mental disorders, and its use develops psychotic symptoms. Coke works as an inhibitor of serotonin and noradrenaline reuptake. The majority of psychotic symptoms are related to cocaine use within 24-48 hours [26, 27]. In sum, it is one of the most favorite drugs among teenagers and can be a serious risk factor and increase the possibility of psychoses in the future [28, 29] (Table 3).

3.8. Kratom

Kratom (Mitragyna speciose) is a psychoactive plant preparation that has medicinally been used for its stimulant effects and as an opioid substitute [30]. It can cause psychosis and even death. But the difference is that kratom’s effect for causing psychosis is stronger than other opioids. It can lead to addiction, sleeping and eating disorders as well. Also, neuropsychiatric side effects such as hallucinations, delusions and paranoia are usual after kratom intake [31] (Table 3).

3.9. Cathinone

Cathinone is related to the phenethylamine family but its potency is much lower than others [32]. It starts to have effects on consumers within 15 minutes at least and 45 minutes at most after injection. By inhaling, the sensations can be experienced within minutes and reach a higher intensity and stronger effect, but the effects last for 2-3 hours in oral and nasal use [33, 34]. This group consists of substances similar to the ones naturally occurring in Catha edulis (Khat) known as cathinone [35] (Table 3).

3.10. Hallucinogens

Hallucinogens include a wide group of natural and synthetic substances. As hallucinations are the intended toxidrome, these substances may cause psychosis. Currently, classic hallucinogens are seen as those that have a psychopharmacological profile similar to mescaline, psilocybin, and lysergic acid diethylamide (LSD) [36]. Classical hallucinogens (psychedelics) can be divided into three main chemical classes: tryptamines (e.g., psilocin), ergolines (e.g., LSD), and phenethylamines (e.g., mescaline). Tryptamines closely resemble serotonin chemically. Psilocybin and mescaline are natural, but LSD and LSD-like are synthetic drugs. It affects the visual cortex, which leads to illusions and open-eye dreams, which is one of the most important psychotic symptoms ref. There are two kinds of perception disorders by using hallucinogens: short-term, in which users do not experience significant impairment; psychiatric care is rarely sought; and long-term, which reflects chronic severe syndrome [37, 38] (Table 3).

3.11. Phencyclidine and Ketamine

These effects can be attributed to dopamine level incretion in the prefrontal cortex, which can be understood by considering the binding of ketamine and PCP to the dopamine receptor 2 (D2) [[39, 40]. Beck and coworkers discovered a noteworthy increase in temporary mental health issues related to ketamine usage [38, 41-43] (Table 3).

3.12. Antibiotics

Surprisingly, some kinds of antibiotics can lead to psychotic disorders (e.g., fluoroquinolones) [44-47] (Table 3).

3.13. Miscellaneous Compounds

Although, these are not the only substances that may lead to psychosis. There are other substances that can lead to psychosis; Dissociative, Sedatives or analgesics, New synthetic opioids (NSOs) (e.g., U-47700, U-49900, AH-7921, U-50488, U-51754, MT-45, Acetylfentanyl, Carfentanyl, Furanylfentanyl) [48], Desomorphine (‘krokodil’), Mitragynine (‘Kratom’, ‘kakuam’, ‘thang’, ‘ketum’, ‘biak’) [49], Salvinorin A (Salvia divinorum, hierba de Maria’, ‘Maria pastora’, ‘Sally-D’, ‘magic mint’) [50], Ketamine-like dissociatives; Ketamine (‘ket’, ‘special K’, ‘super K’, ‘kit-kat’) [51], Phencyclidine (PCP, ‘angel dust’, ‘supergrass’, ‘boat’) and PCP-type substances (e.g., 3- MeO-PCE, 4-MeO-PCP) [52], Methoxetamine (‘mexxy’, ‘special M’), Novel Stimulants and novel psychedelics [53];Synthetic cathinones (e.g., mephedrone, ‘m-cat’; ‘meow’) [54], Psychedelic/empathogenic phenethylamines (e.g., 2C series; D series, such as DOI, DOC; benzodifurans, such as ‘bromodragonfly’; others, such as PMA/PMMA) [55], Piperazines (e.g., BZP, mCPP, ‘party pills’, ‘smileys’) [56], Tryptamines (e.g., DMT, 5- MeO-DMT, ‘magic mushrooms’), Prescription drugs with a misusing potential: 1. ANTIDEPRESSANTS;(Bupropion, Amitriptyline, Venlafaxine (‘baby ecstasy’)) [57], 2. ANTIPSYCHOTICS: (Quetiapine (‘Susie Q,’ ‘Quell,’ and ‘baby heroin’); ‘Q ball’ (quetiapine with cocaine); ‘MaQ ball’ (quetiapine and marijuana), Olanzapine (‘Lilly’)) [58], 3. GABAPENTINOIDS (pregabalin and gabapentin), 4. Z-DRUGS (zaleplon, zolpidem and zopiclone) [59], DESIGNER BENZODIAZEPINES (e.g., clonazolam, etizolam, flubromazepam, phenazepam (‘Zinnie’) and pyrazolam [60], 5. OVER-THE-COUNTER DRUGS: (Codeine [61] (‘Purple drank’ is a mix of codeine and promethazine), Loperamide [62], Dextromethorphan (DXM) [63] for instance [64-72] (Tables 3 and 4).

Table 4.
Psychoactive substances or medications causing secondary psychosis.
Medical Section Category (type)
Psychoactive Substances Alcohol Withdrawal and Hallucinosis, Amphetamine Intoxication, Cocaine Intoxication, Hallucinogen Intoxication, Phencyclidine Intoxication, Sedative Hypnotic Withdrawal
Cardiology Digitalis, Beta-blockers, Antiarrhythmics
Oncology Asparaginase, Cytarabine, Fluorouracil, Ifosfamide, Methotrexate, Vincristine
Infectious diseases Ciprofloxacin, Antitubercular agents, Antimalarials, Antivirals
Neurology Dopamine agonists (amantadine, bromocriptine, and levodopa)
Psychiatry Antidepressants (bupropion, tricyclic antidepressants), Anticholinergics (benztropine, diphenhydramine)
Gastroenterology Cimetidine, Ranitidine
Analgesia Pentazocine, Meperidine, Indomethacin
Genera Corticosteroids, Metrizamide, Methysergide, Baclofen Ephedrine

4. DISCUSSION

In the last two decades, plenty of research has been dedicated to psychosis induced by cannabinoids, psychostimulants such as methamphetamine, amphe- tamine, methylphenidate and cocaine, hallucinogens and so on. Despite the apparent connection to psychotic symptoms, the scientific community is still unable to give definitive proof on this specific subject. The main point about the subject is that there has been a notable rise in both the quantity and diversity of newly developed psychoactive drugs. Over time, more powerful have been formulated and circulated, resulting in more harmful side effects and more severe impacts on the body. This surge in new drug misuse has greatly expanded the occurrence of secondary psychoses.

For example, synthetic cannabinoids and synthetic cathinone may lead to serious clinical syndrome with a high risk of a fully structured psychotic disorder [73, 74]. Clinicians still face a difficult task in differentiating SIP and primary psychotic illnesses. Nonetheless, we hold optimistic expectations that this research could assist in overcoming the challenge [75, 76].

But despite considerable variation in how substance exposure and psychosis were elicited or defined, there is a notable consistency across the population groups studied in different research. As has been said before, young ages play a big role in drug abuse. The most common reasons are fun or parents’ attitudes. On the other hand, drug abuse may have real side effects on the body and especially the brain as time passes and may lead to psychosis in the future. Although none of these variables, alone or together, can recognize the etiology of psychosis accurately. A combination of approaches is the best management for substance-induced psychosis, which includes medication management, psychological treatment (individual therapy or group therapy), and family engagement in some cases. After all, we have collected as much information as we could about different drugs that may lead to psychosis, psychotic symptoms, and similarities and differences between such substances. Finally, this article has been based on limited evidence, and further study of both pharmacologic and psychological interventions is needed to find out how to provide the best care to vulnerable youth and adults who have experienced such symptoms of psychosis and substance use. Systematic literature reviews are crucial in research articles for several reasons. For example, they provide a comprehensive overview of existing research on a particular topic, helping researchers understand the current state of knowledge. By following a systematic approach, researchers can ensure that the review is unbiased and based on all available evidence, reducing the risk of cherry-picking data. Systematic reviews help identify gaps in the existing literature, highlighting areas where further research is needed. They allow for the evaluation of the quality of individual studies, helping to assess the reliability of the findings. Also, systematic reviews can facilitate meta-analysis, where data from multiple studies are combined to provide more robust conclusions. The results of systematic reviews can inform policy-making, clinical practice, and future research directions. Overall, using systematic literature reviews in articles enhances the credibility and reliability of the research by providing a structured and rigorous synthesis of existing knowledge. The research includes most of the substances that can lead to psychoses, and it is a comprehensive article that can help to identify these substances conveniently. Psychoactive substances and some medications can cause secondary psychosis. For example, Digitalis, Beta-blockers, Antiarrhythmic in cardiology, Asparaginase, Cytarabine, Fluorouracil, Ifosfamide, Methotrexate, Vincristine in oncology, Dopamine agonists (amantadine, bromocriptine, and levodopa) in neurology, Cimetidine, Ranitidine in gastroenterology and Antidepressants (bupropion, tricyclic antidepressants), Anticholinergics (benztropine, diphenhydramine) in psychiatry can cause secondary psychosis (Table 4).

5. LIMITATIONS AND FUTURE DIRECTIONS

This systematic review has some limitations. There are few scientific research and articles about substance-induced psychoses, and it is difficult to say with certainty that these substances lead to psychoses definitely, and these are all of the substances that may lead to psychoses. First of all, this article has been written about humans, and there is nothing certain about humans, and the effects of substances differ from one another. Secondly, there are lots of substances that are undetermined and uncharted. Also, there will be more human-made substances in the future. Further studies and investigations are required to verify these substances and to find antidotes and cures for substance-induced psychotic patients as well. Finally, this research can only represent the situation of a single part of the whole world population.

CONCLUSION

A few studies indicate that there are a few substances and even medicines that may lead to psychoses with high possibility. Numerous psychological intervention strategies for SIPs show promising treatment results, indicating the potential for customizable interventions that can meet individual needs. It can be concluded that the etiology of psychoses is different. Psychoses can develop because of sad experiences in childhood, available genes, depressing experiences and accidents, some medicines for a long time, or drug misuse. However, the most common reasons are available genes and substances that have been discussed. Unfortunately, these substances change the chemical structures of genes and can lead to other disorders and diseases besides psychoses. However, additional research is needed to effectively put these strategies into practice in interventions that are supported by a reliable mechanism of change and to verify the effectiveness of those interventions.

AUTHORS' CONTRIBUTIONS

Research design: Isaac Karimi

Data collection: Nioosha Pooyanmehr

Writing the manuscript: Nioosha Pooyanmehr

Primary revision: Isaac Karimi

LIST OF ABBREVIATIONS

DSM = Diagnostic and Statistical Manual
SIP = Substance-induced Psychosis
THC = Tetrahydrocannabinol
CBD = Cannabidiol
LSD = Lysergic Acid Diethylamide

CONSENT FOR PUBLICATION

Not applicable.

STANDARDS OF REPORTING

PRISMA guidelines have been followed.

AVAILABILITY OF DATA AND MATERIALS

All the data and supporting information is provided within the article.

FUNDING

None.

CONFLICT OF INTEREST

Hereby, it has been announced that the authors have no conflict of interest.

ACKNOWLEDGEMENTS

Declared none.

SUPPLEMENTARY MATERIAL

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.

REFRENCES

1
Fiorentini A, Volonteri LS, Dragogna F, et al. Substance-induced psychoses: A critical review of the literature. Curr Drug Abuse Rev 2011; 4(4): 228-40.
2
Kret ME, Ploeger A. Emotion processing deficits: A liability spectrum providing insight into comorbidity of mental disorders. Neurosci Biobehav Rev 2015; 52: 153-71.
3
Sunshine A, McClellan J. Practitioner review: Psychosis in children and adolescents. J Child Psychol Psychiatry 2023; 64(7): 980-8.
4
Schifano F, Napoletano F, Chiappini S, et al. New/emerging psychoactive substances and associated psychopathological consequences. Psychol Med 2021; 51(1): 30-42.
5
Fiorentini A, Cantù F, Crisanti C, Cereda G, Oldani L, Brambilla P. Substance-induced psychoses: An updated literature review. Front Psychiatry 2021; 12: 694863.
6
Brown HE, Kaneko Y, Donovan AL. Substance-induced psychosis and co-occurring psychotic disorders. In: Donovan A, Bird S, Eds. Substance Use and the Acute Psychiatric Patient Current Clinical Psychiatry 2019.
7
Barrett FS. Comparative pharmacology and circuit-level models of the effects of psychedelic drugs on the human brain. Biol Psychiatry Cogn Neurosci Neuroimaging 2022; 7(9): 849-51.
8
Clausen L, Hjorthøj CR, Thorup A, et al. Change in cannabis use, clinical symptoms and social functioning among patients with first-episode psychosis: A 5-year follow-up study of patients in the OPUS trial. Psychol Med 2014; 44(1): 117-26.
9
Gurillo P, Jauhar S, Murray RM, MacCabe JH. Does tobacco use cause psychosis? Systematic review and meta-analysis. Lancet Psychiatry 2015; 2(8): 718-25.
10
Gage SH, Munafò MR. Rethinking the association between smoking and schizophrenia. Lancet Psychiatry 2015; 2(2): 118-9.
11
Riggs DW, Pearce R, Pfeffer CA, Hines S, White F, Ruspini E. Transnormativity in the psy disciplines: Constructing pathology in the diagnostic and statistical manual of mental disorders and standards of care. Am Psychol 2019; 74(8): 912-24.
12
Mauri MC, Di Pace C, Reggiori A, Paletta S, Colasanti A. Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up. Asian J Psychiatr 2017; 29: 117-22.
13
Bewley-Taylor DR, Nougier M. Measuring the ‘world drug problem’: 2019 and beyond.Collapse of the Global Order on Drugs: From UNGASS 2016 to Review 2019 2018; 65-83.
14
Oomen PP, van Hell HH, Bossong MG. The acute effects of cannabis on human executive function. Behav Pharmacol 2018; 29(7): 605-16.
15
Bhattacharyya S, Fusar-Poli P, Borgwardt S, et al. Modulation of mediotemporal and ventrostriatal function in humans by Δ9-tetrahydrocannabinol: A neural basis for the effects of Cannabis sativa on learning and psychosis. Arch Gen Psychiatry 2009; 66(4): 442-51.
16
Smart R, Caulkins JP, Kilmer B, Davenport S, Midgette G. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state. Addiction 2017; 112(12): 2167-77.
17
ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in cannabis potency over the last 2 decades (1995–2014): Analysis of current data in the United States. Biol Psychiatry 2016; 79(7): 613-9.
18
Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): A multicentre case-control study. Lancet Psychiatry 2019; 6(5): 427-36.
19
Organization WH. Global status report on alcohol and health 2018 2019; 4-6.
20
Organization WH. Alcohol policy impact case study: The effects of alcohol control measures on mortality and life expectancy in the Russian Federation 2019; 8-12.
21
Cather C, Pachas GN, Cieslak KM, Evins AE. Achieving smoking cessation in individuals with schizophrenia: Special considerations. CNS Drugs 2017; 31(6): 471-81.
22
Fluyau D, Mitra P, Lorthe K. Antipsychotics for amphetamine psychosis. A systematic review. Front Psychiatry 2019; 10: 740.
23
Paul S, Abbas MS, et al. Psychosis induced by methylphenidate in children and young patients with attention-deficit hyperactivity disorder. Cureus 2023; 15(1): e34299.
24
Walichniewicz P, Lew-Starowicz M. Methylphenidate-induced psychosis in a young antipsychotic-naïve female patient. Wiedza Medyczna 2021; 3(1): 28-31.
25
Karsinti E, Labaeye M, Piani K, et al. Network analysis of psychotic manifestations among cocaine users. J Psychiatr Res 2020; 130: 300-5.
26
Sabe M, Zhao N, Kaiser S. A systematic review and meta-analysis of the prevalence of cocaine-induced psychosis in cocaine users. Prog Neuropsychopharmacol Biol Psychiatry 2021; 109: 110263.
27
Zerdazi EH, Curis E, Karsinti E, et al. Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors. Drug Alcohol Depend 2022; 232: 109270.
28
Hides L, Chan G, Dawe S, et al. Direction of the relationship between methamphetamine use and positive psychotic symptoms in regular methamphetamine users: Evidence from a prospective cohort study. Br J Psychiatry 2021; 219(1): 361-7.
29
Boden JM, Foulds JA, Newton-Howes G, McKetin R. Methamphetamine use and psychotic symptoms: Findings from a New Zealand longitudinal birth cohort. Psychol Med 2023; 53(3): 987-94.
30
Cutlip HA, Bushman E, Thottumari L, Mogallapu R, Ang-Rabanes M. A case report of kratom-induced psychosis. Cureus 2021; 13(6): e16073.
31
Sablaban IM, Gautam M. Kratom & stimulant co-addiction: A case series and brief review. J Addict Dis 2022; 7: 1-4.
32
Lee PY, Hsu CC, Chan CH. Synthetic cathinone–induced myocarditis and psychosis: A case report. J Addict Med 2023; 17(2): e135-7.
33
Daziani G, Lo Faro AF, Montana V, et al. Synthetic cathinones and neurotoxicity risks: A systematic review. Int J Mol Sci 2023; 24(7): 6230.
34
Skowronek R, Skowronek A, et al. Suicides under the influence of synthetic cathinones. J Psychia Clin Psychol 2021; 21(4): 245.
35
Kuropka P, Zawadzki M, Szpot P. A narrative review of the neuropharmacology of synthetic cathinones—Popular alternatives to classical drugs of abuse. Hum Psychopharmacol 2023; 38(3): e2866.
36
Dellazizzo L, Giguère S, Léveillé N, Potvin S, Dumais A. A systematic review of relational-based therapies for the treatment of auditory hallucinations in patients with psychotic disorders. Psychol Med 2022; 52(11): 2001-8.
37
Schutte MJL, Linszen MMJ, Marschall TM, et al. Hallucinations and other psychotic experiences across diagnoses: A comparison of phenomenological features. Psychiatry Res 2020; 292: 113314.
38
Brambilla P, Mauri MC, Altamura AC. Hallucinations in psychoses and affective disorders: A clinical and biological approach. Psychiatry 2018; 1-208.
39
Beck K, Hindley G, Borgan F, et al. Association of ketamine with psychiatric symptoms and implications for its therapeutic use and for understanding schizophrenia: A systematic review and meta-analysis. JAMA Netw Open 2020; 3(5): e204693-3.
40
Ham S, Kim TK, Chung S, Im HI. Drug abuse and psychosis: New insights into drug-induced psychosis. Exp Neurobiol 2017; 26(1): 11-24.
41
Hashimoto K. Ketamine: Anesthetic, psychotomimetic, antidepressant, or anthelmintic? Mol Psychiatry 2022; 27(8): 3116-8.
42
Lazzaretti M, et al. Substances of abuse and hallucinogenic activity: The serotoninergic pathway-focus on classical hallucinogens and entactogens. Hallu Psych Affect Disord A ClinBiol Appr 2018; 17-31.
43
Hermle L, Spitzer M, Borchardt D, Kovar KA, Gouzoulis E. Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents? Neuropsychopharmacology 1993; 8(2): 171-6.
44
Sellick J, Mergenhagen K, Morris L, et al. Fluoroquinolone-related neuropsychiatric events in hospitalized veterans. Psychosomatics 2018; 59(3): 259-66.
45
Neufeld NH, Mohamed NS, Grujich N, Shulman K. Acute neuropsychiatric symptoms associated with antibiotic treatment of Helicobacter pylori infections: A review. J Psychiatr Pract 2017; 23(1): 25-35.
46
Mostafa S, Miller BJ. Antibiotic-associated psychosis during treatment of urinary tract infections: A systematic review. J Clin Psychopharmacol 2014; 34(4): 483-90.
47
Xiao M, Huang X. Unmasking antibiotic-associated neurological disorders: The underminer in Intensive Care Unit. J Clin Neurosci 2021; 91: 131-5.
48
Marchei E, Pacifici R, Mannocchi G, Marinelli E, Busardò FP, Pichini S. New synthetic opioids in biological and non-biological matrices: A review of current analytical methods. Trends Analyt Chem 2018; 102: 1-15.
49
Liu L, Wheeler SE, Venkataramanan R, et al. Newly emerging drugs of abuse and their detection methods: An ACLPS critical review. Am J Clin Pathol 2018; 149(2): 105-16.
50
Ventura L, Carvalho F, Dinis-Oliveira RJ. Opioids in the frame of new psychoactive substances network: A complex pharmacological and toxicological issue. Curr Mol Pharmacol 2018; 11(2): 97-108.
51
Orsolini L, Chiappini S, Corkery JM, Guirguis A, Papanti D, Schifano F. The use of new psychoactive substances (NPS) in young people and their role in mental health care: A systematic review. Expert Rev Neurother 2019; 19(12): 1253-64.
52
Baumeister D, Tojo LM, Tracy DK. Legal highs: staying on top of the flood of novel psychoactive substances. Ther Adv Psychopharmacol 2015; 5(2): 97-132.
53
Wallach J, Brandt SD. 1, 2-Diarylethylamine-and ketamine-based new psychoactive substances. New Psychoactive Substances: Pharmacology. Clin Forens Analyt Toxicol 2018; 305-52.
54
Prosser JM, Nelson LS. The toxicology of bath salts: A review of synthetic cathinones. J Med Toxicol 2012; 8(1): 33-42.
55
Miliano C, Serpelloni G, Rimondo C, Mereu M, Marti M, De Luca MA. Neuropharmacology of new psychoactive substances (NPS): Focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants. Front Neurosci 2016; 10: 153.
56
Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol 2012; 8(1): 15-32.
57
Evans EA, Sullivan MA. Abuse and misuse of antidepressants. Subst Abuse Rehabil 2014; 5: 107-20.
58
Klein L, Bangh S, Cole J. Intentional recreational abuse of quetiapine compared to other second-generation antipsychotics. West J Emerg Med 2017; 18(2): 243-50.
59
Bonnet U, Richter EL, Isbruch K, Scherbaum N. On the addictive power of gabapentinoids: A mini-review. Psychiatr Danub 2018; 30(2): 142-9.
60
Moosmann B, King LA, Auwärter V. Designer benzodiazepines: A new challenge. World Psychiatry 2015; 14(2): 248.
61
Cooper RJ. ‘I can’t be an addict. I am.’ Over-the-counter medicine abuse: A qualitative study. BMJ Open 2013; 3(6): e002913.
62
Schifano F, Chiappini S. Is there such a thing as a ‘lope’ dope? Analysis of loperamide-related European Medicines Agency (EMA) pharmacovigilance database reports. PLoS One 2018; 13(10): e0204443.
63
Wilson MD, Ferguson RW, Mazer ME, Litovitz TL. Monitoring trends in dextromethorphan abuse using the National Poison Data System: 2000–2010. Clin Toxicol 2011; 49(5): 409-15.
64
Martinotti G, et al. Novel psychoactive substances and induced phenomena in psychopathology: The lysergic psychoma. J Psychopathol 2015; 21(4): 400-5.
65
Crone C, Fochtmann LJ, Attia E, et al. The american psychiatric association practice guideline for the treatment of patients with eating disorders. Am J Psychiatry 2023; 180(2): 167-71.
66
Sigvard AK, Nielsen MØ, Gjedde A, et al. Dopaminergic activity in antipsychotic-naïve patients assessed with positron emission tomography before and after partial dopamine D2 receptor agonist treatment: Association with psychotic symptoms and treatment response. Biol Psychiatry 2022; 91(2): 236-45.
67
Beck K, Arumuham A, Brugger S, et al. The association between N -methyl- d -aspartate receptor availability and glutamate levels: A multi-modal PET-MR brain imaging study in first-episode psychosis and healthy controls. J Psychopharmacol 2022; 36(9): 1051-60.
68
Eggers AE. A serotonin hypothesis of schizophrenia. Med Hypotheses 2013; 80(6): 791-4.
69
Selvaraj S, Arnone D, Cappai A, Howes O. Alterations in the serotonin system in schizophrenia: A systematic review and meta-analysis of postmortem and molecular imaging studies. Neurosci Biobehav Rev 2014; 45: 233-45.
70
de Bartolomeis A, Barone A, Begni V, Riva MA. Present and future antipsychotic drugs: A systematic review of the putative mechanisms of action for efficacy and a critical appraisal under a translational perspective. Pharmacol Res 2022; 176: 106078.
71
Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry 2001; 158(3): 360-9.
72
Serrano WC, Maldonado J. The use of physostigmine in the diagnosis and treatment of anticholinergic toxicity after olanzapine overdose: Literature review and case report. J Acad Consultliais Psychiat 2021; 62(3): 285-97.
73
Chiappini S, Mosca A, Miuli A, et al. New psychoactive substances and suicidality: A systematic review of the current literature. Medicina 2021; 57(6): 580.
74
Alves VL, Gonçalves JL, Aguiar J, Teixeira HM, Câmara JS. The synthetic cannabinoids phenomenon: From structure to toxicological properties. A review. Crit Rev Toxicol 2020; 50(5): 359-82.
75
Shah D, Chand P, Bandawar M, Benegal V, Murthy P. Cannabis induced psychosis and subsequent psychiatric disorders. Asian J Psychiatr 2017; 30: 180-4.
76
Valmaggia LR, Day FL, Jones C, et al. Cannabis use and transition to psychosis in people at ultra-high risk. Psychol Med 2014; 44(12): 2503-12.