Methamphetamine and Psychosis

The experimental reproduction of amphetamine psychosis.
Bell, David S
Archives of General Psychiatry, Vol. 29(1), Jul, 1973. pp. 35-40.
Abstract:
Administered a large dose of methamphetamine hydrochloride, iv, to 16 15-41 yr old amphetamine-dependent psychiatric inpatients. Results show that methamphetamine reproduced the amphetamine psychosis in 12 of 14 Ss dependent on amphetamine sulfate, and failed to produce a psychosis in 2 Ss who were eventually found to have not used amphetamine regularly above the therapeutic dose range. The psychosis was the facsimile of the disorder observed during drug abuse: a schizophrenic-like state of paranoia in a setting of clear consciousness accompanied by auditory and/or visual hallucinations, but without thought disorder. In some cases the onset of the psychosis was sudden and occurred within 1 hr of commencing the iv injection. This finding suggests that hypotheses about depletion of catecholamines and long-term metabolites may need to be reconsidered.

Relapse of Paranoid Psychotic State in Methamphetamine Model of Schizophrenia.
Sato, Mitsumoto, et al.
Schizophrenia Bulletin, Vol 18(1), 1992. pp. 115-122.
Abstract:
The study of the clinical course of methamphetamine (MAP) psychosis yields insights into the biological aspect of the relapse of the paranoid psychotic state with hallucination in schizophrenia. A series of MAP psychosis studies in Japan conducted over a period of more than four decades revealed three types of clinical courses of MAP psychosis after discontinuation of MAP: transient type, prolonged type, and persistent type. Identification of the latter two indicates a lasting change in the brain that produces and maintains a schizophrenia-like paranoid psychotic state without MAP. The characteristic course seen in the transient type is acute recurrence of the psychotic state after a long remission period, almost identical to the initial episode, due to reuse of MAP or to psychological stressors. Such lasting vulnerability of the brain to schizophrenia-like psychotic symptoms may be caused by a lasting sensitization of the brain to the psychotogenic action of MAP resulting from its chronic abuse. Experimental studies using animals sensitized to MAP-induced stereotypy suggest that lasting enhancement of MAP-induced dopamine release in the striatum and nucleus accumbens is related to the development and expression of brain vulnerability to schizophrenic symptoms.

Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats.
Watanabe, Takemi, et al.
Behavioural Brain Research, Vol 93(1-2), Jun, 1998. pp. 119-129.
Abstract:
To investigate the role of the ventral tegmental area (VTA) in paranoid psychosis, an analysis of the behavioral responses induced by electrical stimulation of the VTA in male rats was made. Abnormal behavior induced by bilateral high-frequency VTA stimulation consisted of 2 components: forward locomotion and exploration. Similar responses were obtained when the nucleus accumbens or prefrontal cortex were stimulated. The expression of behavioral responses to VTA stimulation was significantly attenuated by dopamine receptor or antagonists. These results indicate that VTA stimulation causes a transient hyperdopaminergic state in the brain that resembles psychostimulant-induced abnormal behavior. The effects of chronic administration of methamphetamine (MAP) on the behavioral responses to VTA stimulation were also investigated. Although an acute administration of MAP did not affect the behavioral responses to VTA stimulation, chronic treatment with MAP caused a long-lasting reduction in the electrical threshold for the induction of abnormal behavior, compared with chronic saline-treated rats. It is suggested that a lasting enhancement in the behavioral response to stimulation of VTA neurons may contribute to the etiology of paranoid schizophrenia and amphetamine psychosis.

Methamphetamine and driving impairment.
Logan, B. K.
Journal of Forensic Sciences, Vol 41(3), May, 1996. pp. 457-464.
Abstract:
Following a review of the effects of methamphetamine (MAMP) on human performance, driving and behavior were evaluated in 28 cases in which drivers arrested or killed in traffic accidents had tested positive for MAMP. Circumstances surrounding the arrest or accident were examined, as were arresting officers’ observations of behavioral irregularities. Most arrests resulted from accidents in which the driver was determined to be culpable. Typical driving behaviors included drifting out of the lane of travel, erratic driving, weaving, speeding, drifting off the road, and high speed collisions. Behavioral manifestations of MAMP use in arrestees included rapid or confused speech, rapid pulse, agitation, paranoia, dilated pupils, and violent or aggressive attitude. Combined alcohol and MAMP use was uncommon, but use of marijuana was evident in about one-third of the cases.

Spontaneous recurrence of methamphetaminepsychosis: Increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic change.
Yui, K., et al.
European Archives of Psychiatry and Clinical Neuroscience, Vol 249(2), 1999. pp. 103-111.
Abstract:
Studied the factors precipitating spontaneous recurrences of methamphetamine (MAP)-induced paranoid-hallucinatory states (referred to as flashbacks). Ss were 87 female inmates. 46 Ss had a history of MAP psychosis; 28 experienced flashbacks and 18 did not. Plasma levels of catecholamines and their metabolites were assayed in the 28 flashbackers, the 18 non-flashbackers, 8 Ss with persistent MAP psychosis, and 33 control Ss. The flashbackers had been exposed to significantly higher numbers of stressful events, and/or MAP-induced frightening paranoid-hallucinatory states during previous MAP use, than the non-flashbackers. Factors triggering the flashbacks met the Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) criteria for a mild psychosocial stressor. During flashbacks, plasma norepinephrine levels increased and plasma levels of 3-methoxytyramine, which is an indicator of dopamine release, showed a smaller increase. It follows that stressful experiences together with MAP use may induce sensitization to mild psychosocial stressors. Noradrenergic hyperactivity and some degree of increased dopamine release may be involved in this process. Stress sensitization may elicit memories of MAP psychosis associated with stressful experiences in response to mild psychosocial stressors, leading to the occurrence of flashbacks.

History of the methamphetamine problem.
Anglin, M. Douglas, et al.
Journal of Psychoactive Drugs, Vol 32(2), Apr-Jun, 2000. Special Issue: The
Abstract:
Methamphetamine (MA) is a derivative of amphetamine, which was widely prescribed in the 1950s and 1960s as a medication for depression and obesity, reaching a peak of 31 million prescriptions in the United States in 1967. Until the late 1980s, illicit use and manufacture of MA was endemic to California, but the MA user population has recently broadened in nature and in regional distribution, with increased use occurring in midwestern states. An estimated 4.7 million Americans have tried MA at some time in their lives. Short-and longterm health effects of MA use include stroke, cardiac arrhythmia, stomach cramps, shaking, anxiety, insomnia, paranoia, hallucinations, and structural changes to the brain. Children of MA abusers are at risk of neglect and abuse, and the use of MA by pregnant women can cause growth retardation, premature birth, and developmental disorders in neonates and enduring cognitive deficits in children. MA-related deaths and admissions to hospital emergency rooms are increasing. Although inpatient hospitalization may be indicated to treat severe cases of long-term MA dependence, optimum treatment for MA abusers relies on an intensive outpatient setting with three to five visits per week of comprehensive counseling for at least the first three months.

Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states in female subjects: Susceptibility to psychotic states and implications for relapse of schizophrenia.
Yui, Kunio, et al.
Pharmacopsychiatry, Vol 35(2), Mar, 2002. pp. 62-71.
Abstract:
Examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks). Plasma monoamine metabolite levels were assayed in 19 flashbackers (FBs); 20 non-FBs with a history of MAP psychosis; 8 Ss with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 FBs had undergone frightening and stressful experiences during previous MAP use. Mild stressors triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine–an index of dopamine (DA) release. Among the 19 FBs, 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while 11 with 1 episode displayed small increases in NE and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased DA release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization and also noradrenergic hyperactivity and enhanced DA release.

Exploring the Methamphetamine Explosion among San Diego Arrestees.
Yacoubian, George S.
Journal of Alcohol and Drug Education, Vol 49(1), Mar, 2005. pp. 7-19.
Abstract:
Explores the methamphetamine explosion among San Diego arrestees. Developed primarily in clandestine laboratories, methamphetamine, also known as ‘ice’ or ‘crank,’ is a highly addictive and easily manufactured synthetic drug. Physical effects include pupil dilation, hyperactivity, euphoria, tremors, and a sense of increased energy. Methamphetamine use increases the heart rate, blood pressure, and body temperature. Chronic abuse produces a psychosis similar to schizophrenia and is characterized by paranoia, self absorption, and auditory and visual hallucinations. Erratic and violent behavior is frequently witnessed among chronic, high-dose methamphetamine abusers. Previous studies suffer from several limitations. None of the studies presented empirical findings, either from a primary data collection effort or a secondary analysis. To address these limitations, we turn to data from the Arrestee Drug Abuse Monitoring (ADAM) Program. The ADAM Program was established by the National Institute of Justice in 1987. An exploration of methamphetamine-positive rates among ADAM sites between 1991 and 2001 indicate that its use is concentrated within the Western part of the United States. Three study limitations were be noted.

Amphetamine use and co-occurring psychological problems: Review of the literature and implications for treatment.
Baker, A., Dawe, S.
Australian Psychologist, Vol 40(2), Jun, 2005. pp. 88-95.
Abstract:
There has been a substantial increase in the use of amphetamine in Australia in recent years, with many users presenting with a range of psychological symptoms including those associated with mood, anxiety and psychotic disorders. Many of these symptoms are due to the direct effect of amphetamine or occur during withdrawal and resolve rapidly. However, determining whether there is a pre-existing disorder requires a careful assessment of the temporal relationship between the onset of regular drug use and symptoms, and ideally ongoing monitoring of symptoms in the absence of drug use. Treatment options need to match the diagnostic presentation, and drawing from the limited literature in this area it is recommended that amphetamine use be targeted in the first instance and other more intensive treatments follow as the diagnostic picture becomes clearer. Many people use psychostimulants and, although the majority who use occasionally by non-injecting routes of administration do not experience problems (Hall, Darke, Ross, & Wodak, 1993), it appears that as many as 30% of amphetamine users develop a psychostimulant use disorder (Hall, Teesson, Lynskey, & Degenhardt, 1998). Of particular concern is the recent increase in the use of methamphetamine across Australia (Topp, Day, & Degenhardt, 2003), a synthetic drug closely related to amphetamine but with higher abuse potential. It produces euphoric effects that are similar to, but longer lasting than those of, cocaine (Dean, 2004), with some evidence suggesting that the progression from initial use to regular and problematic use occurs more rapidly than with cocaine use (Castro, Harrington, Walton, & Rawson, 2000). There are many indications (e.g., increased availability of methamphetamine, an increasing trend towards injection, an increase in demand for treatment and reports of additional demands for emergency services) that the increase in methamphetamine use in Australia in the last 5 years will continue (Jenner & McKetin, 2004). There are now a number of studies in which the range of psychological symptoms have been documented among amphetamine users including depressed mood, anxiety, irritability, paranoia, mood swings, difficulty concentrating, aggression, hallucinations and psychosis (Topp et al., 2003). It would appear that many of these symptoms are related to the use of amphetamine and abate on cessation of use. Cross-sectional studies have suggested that perhaps up to half of regular amphetamine users report that these symptoms emerge after the commencement of regular amphetamine use (Baker et al., submitted; Hall, Hando, Darke, & Ross, 1996). However, it is possible that some symptoms may have pre-dated the use of amphetamine and may be related to the initial use of the substance. The risk of experiencing adverse effects of amphetamine appears to be related to dose, with the risk of harm reduced with less than twice weekly use and the use of small amounts (Hall & Hando, 1994). In this paper we review the literature describing the prevalence and course of the most common co-occurring psychological problems among amphetamine users. A review of treatments currently considered to be best practice will be provided and recommendations for further research suggested.

 

An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder.
Suzuki, Atsuko, et al.
Psychiatric Genetics, Vol 16(4), Aug, 2006. pp. 133-138.
Abstract:
Objective: A series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetaminepsychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. Basic methods: We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. Main results: We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P = 0.018, odds ratio = 1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. Conclusions: Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.

Methamphetamine use among young adults: Health and social consequences.
Sommers, Ira, et al.
Addictive Behaviors, Vol 31(8), Aug, 2006. pp. 1469-1476.
Abstract:
The current research analyzed the relationship between methamphetamine use and health and social outcomes. Interviews were conducted with a sample of 106 respondents. Virtually all of the respondents experienced negative consequences of methamphetamine use. The most serious, but least prevalent, methamphetamine-related health problem was seizures and convulsions. The most prevalent health effect was weight loss. A substantial number of respondents experienced severe psychological symptoms: depression, hallucinations, and paranoia. Of the 106 respondents, 34.9% had committed violence while under the influence of methamphetamine. The data suggest that methamphetamine-based violence was more likely to occur within private domestic contexts, both family and acquaintance relationships. It is apparent from the findings that methamphetamine use heightens the risk for negative health, psychological, and social outcomes. Having said this, it is crucial to acknowledge that there was no evidence of a single, uniform career path that all chronic methamphetamine users follow. Furthermore, a significant number of sample members experienced limited or no serious social, psychological, or physical dysfunction as a result of their methamphetamine use.

Presence and persistence of psychotic symptoms in cocaine- versus methamphetamine-dependent participants.
Mahoney, James J. III, et al.
The American Journal on Addictions, Vol 17(2), Mar, 2008. pp. 83-98.
Abstract:
The primary objective of this study was to compare and contrast psychotic symptoms reported by cocaine- and methamphetamine-dependent individuals. Participants included 27 cocaine-dependent and 25 methamphetamine-dependent males, as well as 15 cocaine-dependent and 18 methamphetamine-dependent females. After screening, participants were excluded if they met criteria for any Axis I diagnosis other than nicotine dependence, or methamphetamine or cocaine dependence (ie, participants had to use either methamphetamine or cocaine but were excluded if they met dependence criteria for both). The participants were administered the newly developed Psychotic Symptom Assessment Scale (PSAS), which assesses psychotic symptoms. A high proportion of both cocaine- and methamphetamine-dependent men and women reported delusions of paranoia and auditory hallucinations. However, during the abstinent and intoxicated conditions, methamphetamine-dependent men and women were more likely than cocaine-dependent men and women to report psychotic symptoms. Future studies will compare psychotic symptoms reported by non-dependent recreational stimulant users to stimulant-dependent individuals.

Methamphetamine and paranoia: The Methamphetamine Experience Questionnaire.
Leamon, Martin H., et al.
The American Journal on Addictions, Vol 19(2), Mar-Apr, 2010. pp. 155-168.
Abstract:
Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA‐induced paranoia. We administered the MEQ to 274 MA‐dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA‐induced paranoia, respectively). Test‐retest and inter‐rater reliability for MA‐induced paranoia showed substantial agreement (kappa = .77, p < .05 and kappa = .80, p < .05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p < .05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use.

Clinical features of methamphetamine‐induced paranoia and preliminary genetic association with DBH‐1021C→T in a Thai treatment cohort.
Kalayasiri, Rasmon, et al.
Addiction, Vol 109(6), Jun, 2014. pp. 965-976.
Abstract:
Aims: To explore the clinical features of methamphetamine‐induced paranoia (MIP) and associations between MIP and a genetic polymorphism in dopamine β‐hydroxylase (DBH‐1021C→T). Design: Retrospective analysis of clinical presentation and genetic association by χ2 test and logistic regression analysis. Setting: A Thai substance abuse treatment center. Participants: A total of 727 methamphetamine‐dependent (MD) individuals. Measurements Clinical: Semi‐Structured Assessment for Drug Dependence and Alcoholism (SSADDA) and the Methamphetamine Experience Questionnaire (MEQ). Genetic: DBH‐1021C→T. Findings: Forty per cent of individuals (289 of 727; 39.8%) with MD had MIP. Within‐binge latency to MIP onset occurred more rapidly in the most recent compared with initial MIP episode (P = 0.02), despite unchanging intake (P = 0.89). Individuals with MIP were significantly less likely to carry lower (TT/CT) compared with higher (CC) activity genotypes (34.3 versus 43.3%; χ21 = 5, P = 0.03). DBH effects were confirmed [odds ratio (OR) = 0.7, P = 0.04] after controlling for associated clinical variables (MD severity, OR = 3.4, P < 0.001; antisocial personality disorder, OR = 2.2, P < 0.001; alcohol dependence, OR = 1.4, P = 0.05; and nicotine dependence, OR = 1.4, P = 0.06). TT/CT carriers were more likely to initiate cigarette smoking (OR = 3.9, P = 0.003) and probably less likely to be dependent on alcohol (OR = 0.6, P = 0.05). Conclusions: Among methamphetamine‐dependent individuals, paranoia appears to occur increasingly rapidly in the course of a session of methamphetamine use. Severity of methamphetamine dependence and antisocial personality disorder predicts methamphetamine‐induced paranoia. The genetic polymorphism in dopamine β‐hydroxylase is associated with methamphetamine‐induced paranoiaand influences smoking initiation.

Correlates of transient versus persistent psychotic symptoms among dependent methamphetamine users.
McKetin, Rebecca, et al.
Psychiatry Research, Vol 238, Apr 30, 2016. pp. 166-171.
Abstract:
This study examined correlates of transient versus persistent psychotic symptoms among people dependent on methamphetamine. A longitudinal prospective cohort study of dependent methamphetamine users who did not meet DSM-IV criteria for lifetime schizophrenia or mania. Four non-contiguous one-month observation periods were used to identify participants who had a) no psychotic symptoms, (n = 110); (b) psychotic symptoms only when using methamphetamine (transient psychotic symptoms, n = 85); and, (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent psychotic symptoms, n = 37). Psychotic symptoms were defined as a score of 4 or greater on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content. Relative no psychotic symptoms, both transient and persistent psychotic symptoms were associated with childhood conduct disorder and comorbid anxiety disorders. Earlier onset methamphetamine use and being male were more specifically related to transient psychotic symptoms, while a family history of a primary psychotic disorder and comorbid major depression were specifically related to persistent psychotic symptoms. We conclude that there are overlapping but also distinct clinical correlates of transient versus persistent psychotic symptoms, suggesting potentially heterogeneous etiological pathways underpinning the psychotic phenomena seen amongst people who use methamphetamine.

Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders.
McKetin, Rebecca, et al.
Psychiatry Research, Vol 251, May, 2017. pp. 349-354.
Abstract:
We examined the lifetime experience of hallucinations and delusions associated with transient methamphetamine-related psychosis (MAP), persistent MAP and primary psychosis among a cohort of dependent methamphetamineusers. Participants were classified as having (a) no current psychotic symptoms, (n = 110); (b) psychotic symptoms only when using methamphetamine (transient MAP, n = 85); (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent MAP, n = 37), or (d) meeting DSM-IV criteria for lifetime schizophrenia or mania (primary psychosis, n = 52). Current psychotic symptoms were classified as a score of 4 or more on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content in the past month. Lifetime psychotic diagnoses and symptoms were assessed using the Composite International Diagnostic Interview. Transient MAP was associated with persecutory delusions and tactile hallucinations (compared to the no symptom group). Persistent MAP was additionally associated with delusions of reference, thought interference and complex auditory, visual, olfactory and tactile hallucinations, while primary psychosis was also associated with delusions of thought projection, erotomania and passivity. The presence of non-persecutory delusions and hallucinations across various modalities is a marker for persistent MAP or primary psychosis in people who use methamphetamine.

Methamphetamine psychosis: Insights from the past.
McKetin, Rebecca
Addiction, Mar 8, 2018.
Abstract:
Background and aims To review early case reports and experimental inductions of amphetamine and methamphetamine psychosis, prior to the prohibition of these drugs, to gain a better understanding of the nature and aetiology of methamphetamine psychosis. Methods Papers considered were historical case reports and case series of psychosis relating to the use and misuse of prescription amphetamine, focusing upon papers by Young & Scoville (1938), Connell (1958), and three subsequent experimental studies published in the early 1970s (Griffith 1972, Angrist & Gershon 1970 and Bell 1973), where psychosis was induced in volunteers using high‐dose amphetamine and methamphetamine. Results High‐dose methamphetamine and amphetamine can result in a paranoid psychosis which remits rapidly (within days) of discontinuing use. The central feature is paranoiaoccurring in a clear state of consciousness. This may be accompanied by other psychotic symptoms (e.g. hallucinations). Pre‐existing schizophrenia is not necessary, and the syndrome is not due to sleep deprivation. Conclusions Research findings from the 1930s to the 1970s suggest that paranoid psychosis should be considered a probable consequence of high‐dose methamphetamine use. Individuals who experience psychotic symptoms for any substantive period after intoxication has ended should be suspected of having a functional non‐organic psychosis, or a latent vulnerability thereto.