Stimulant psychosis is a

mental disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...

characterized by

psychotic Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior t ...

symptoms (such as

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...

s, paranoid ideation,

delusion A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or som ...

disorganized thinking A thought disorder (TD) is any disturbance in cognition that adversely affects language and thought content, and thereby communication. A variety of thought disorders were said to be characteristic of people with schizophrenia. A content-though ...

, grossly disorganized behaviour) which involves and typically occurs following an overdose or several day 'binge' on psychostimulants; however, it has also been reported to occur in approximately 0.1% of individuals, within the first several weeks after starting amphetamine or

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

therapy. Methamphetamine psychosis, or long-term effects of stimulant use in the brain (at the molecular level), depend upon genetics and may persist for some time. The most common causative agents are

substituted amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

, including

substituted cathinones Substituted cathinones, which include some stimulants and entactogens, are derivatives of cathinone. They feature a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon, along ...

, as well as certain

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dop ...

s such as

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

and phenidates.

Signs and symptoms

The symptoms of stimulant psychosis vary depending on the drug ingested, but generally involve the symptoms of organic psychosis such as hallucinations, delusions, or

paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy co ...

. Other symptoms may include mania, erratic behavior, agitation and/or aggression.

Cause

Substituted amphetamines

Drugs in the class of amphetamines, or substituted amphetamines, are known to induce "amphetamine psychosis" typically when chronically abused or used in high doses. In an Australian study of 309 active methamphetamine users, 18% had experienced a clinical level psychosis in the past year. Commonly abused amphetamines include methamphetamine,

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

4-FA 4-Fluoroamphetamine (4-FA; 4-FMP; PAL-303; "Flux"), also known as ''para''-fluoroamphetamine (PFA) is a psychoactive research chemical of the phenethylamine and substituted amphetamine chemical classes. It produces stimulant and entactogenic ef ...

, as well as

like a-PVP,

MDPV Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. Its activity at the dopamine tra ...

, and

mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, , White Magic, meow meow, bubble, ''txomin'' and yurrpt. It is chemically similar to the cathinone compounds ...

, though a large number of other closely related compounds have been recently synthesized.

Methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

is sometimes incorrectly included in this class, although it is nonetheless still capable of producing stimulant psychosis. The symptoms of amphetamine psychosis include auditory and visual hallucinations, grandiosity, delusions of persecution, and

delusions of reference Ideas of reference and delusions of reference describe the phenomenon of an individual experiencing innocuous events or mere coincidences and believing they have strong personal significance. It is "the notion that everything one perceives in the ...

concurrent with both clear consciousness and prominent extreme agitation. A Japanese study of recovery from methamphetamine psychosis reported a 64% recovery rate within 10 days rising to an 82% recovery rate at 30 days after methamphetamine cessation. However it has been suggested that around 5–15% of users fail to make a complete recovery in the long term. Furthermore, even at a small dose, the psychosis can be quickly reestablished. Psychosocial stress has been found to be an independent risk factor for psychosis relapse even without further substituted amphetamine use in certain cases. The symptoms of acute amphetamine psychosis are very similar to those of the acute phase of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

although in amphetamine psychosis visual hallucinations are more common and

thought disorder A thought disorder (TD) is any disturbance in cognition that adversely affects language and thought content, and thereby communication. A variety of thought disorders were said to be characteristic of people with schizophrenia. A content-though ...

is rare. Amphetamine psychosis may be purely related to high drug usage, or high drug usage may trigger an underlying vulnerability to schizophrenia. There is some evidence that vulnerability to amphetamine psychosis and schizophrenia may be genetically related. Relatives of methamphetamine users with a history of amphetamine psychosis are five times more likely to have been diagnosed with schizophrenia than relatives of methamphetamine users without a history of amphetamine psychosis. The disorders are often distinguished by a rapid resolution of symptoms in amphetamine psychosis, while schizophrenia is more likely to follow a chronic course. Although rare and not formally recognized, a condition known as Amphetamine Withdrawal Psychosis (AWP) may occur upon cessation of substituted amphetamine use and, as the name implies, involves psychosis that appears on withdrawal from substituted amphetamines. However, unlike similar disorders, in AWP, substituted amphetamines reduce rather than increase symptoms, and the psychosis or mania resolves with resumption of the previous dosing schedule.

Cocaine

Cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

has a similar potential to induce temporary psychosis with more than half of cocaine abusers reporting at least some psychotic symptoms at some point. Typical symptoms include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom. Cocaine-induced psychosis shows sensitization toward the psychotic effects of the drug. This means that psychosis becomes more severe with repeated intermittent use.

Phenidates

and its analogues (such as

ethylphenidate Ethylphenidate (EPH), also known as Baxtercaine in the United Kingdom is a psychostimulant and a close analog of methylphenidate. Ethylphenidate acts as both a dopamine reuptake inhibitor and norepinephrine reuptake inhibitor, meaning it effecti ...

4F-MPH 4-Fluoromethylphenidate (also known as 4-FMPH and 4F-MPH) is a stimulant drug that acts as a higher potency dopamine reuptake inhibitor than the closely related methylphenidate. 4-Fluoromethylphenidate was studied further along with other analog ...

, and

isopropylphenidate Isopropylphenidate (also known as IPH and IPPD) is a piperidine based stimulant drug, closely related to methylphenidate, but with the methyl ester replaced by an isopropyl ester. It has similar effects to methylphenidate but with a longer dura ...

) share similar pharmacological profiles as other norepinephrine-dopamine reuptake inhibitors. Chronic abuse of methylphenidate has the potential to lead to psychosis. Similar psychiatric side effects have been reported in a study of

. No studies regarding psychosis and 4F-MPH or isopropylphenidate have been conducted, but given their high DAT binding and cellular uptake activity, the possibility of stimulant psychosis remains.

Caffeine

There is limited evidence that

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...

, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.

Diagnosis

Differential diagnosis

Though less common than stimulant psychosis, stimulants such as cocaine and amphetamines as well as the dissociative drug

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted percept ...

(PCP, angel dust) may also cause a theorized severe and life-threatening condition known as

excited delirium Excited delirium (ExDS), also known as agitated delirium (AgDS), is a controversial diagnosis sometimes characterized as a potentially fatal state of extreme agitation and delirium. It is typically diagnosed postmortem in young adult males, dispr ...

. This condition manifests as a combination of delirium,

psychomotor agitation Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress. Typical manifestations include ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

s, speech disturbances, disorientation, violent and bizarre behavior, insensitivity to pain, elevated

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

, and hysterical strength."White Paper Report on Excited Delirium Syndrome"
ACEP Excited Delirium Task Force,

American College of Emergency Physicians The American College of Emergency Physicians (ACEP) is a professional organization of emergency medicine physicians in the United States. The organization was founded August 16, 1968, by eight physicians in Lansing, Michigan. ACEP established t ...

, 10 September 2009 Despite some superficial similarities in presentation excited delirium is a distinct (and more serious) condition than stimulant psychosis. The existence of excited delirium is currently debated.

Transition to schizophrenia

A 2019 systematic review and meta-analysis by Murrie et al. found that the pooled proportion of transition from amphetamine-induced psychosis to schizophrenia was 22% (5 studies, CI 14%–34%). This was lower than cannabis (34%) and hallucinogens (26%), but higher than opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.

Treatment

Treatment consists of supportive care during the acute intoxication phase: maintaining hydration, body temperature, blood pressure, and heart rate at acceptable levels until the drug is sufficiently metabolized to allow vital signs to return to baseline. Typical and

atypical antipsychotics The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

have been shown to be helpful in the early stages of treatment. However, the benzodiazepines,

temazepam Temazepam (sold under the brand names Restoril among others) is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hyp ...

and

triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties ...

at 30 mg and 0.5 mg, respectively, are highly effective if aggression, agitation, or violent behaviour is apparent. In the instance of persistent psychosis after repeated use of stimulants, there are cases in which electroconvulsive therapy has been beneficial. This is followed by abstinence from psychostimulants supported with counselling or medication designed to assist the individual preventing a relapse and the resumption of a psychotic state.

References

External links

{{Psychoactive substance use Psychosis Biology of bipolar disorder Amphetamine