DISORDERS DUE TO USE OF STIMULANTS INCLUDING AMPHETAMINES, METHAMPHETAMINE OR METHCATHINONE

1. Definition and nosology

Stimulant use disorders (ICD-11: 6C46; DSM-5-TR: F15.20 Stimulant Use Disorder) — disorders developing from use of amphetamine, methamphetamine, methcathinone and other stimulants. Coded separately: cocaine (6C45), synthetic cathinones including mephedrone (6C47), caffeine (6C48), MDMA or related drugs including MDA (6C4C).

2. History

• Amphetamine first synthesized by Edeleano L. (1887); widespread use in World War II.
• 1950s–1960s — pharmacy-prescription epidemic.
• Methamphetamine epidemic since the 1990s.
• “Bath salts” (synthetic cathinones) — epidemic of 2010+. “Krokodil” (desomorphine) is an opioid and is coded separately in ICD-11 (6C43).

3. Epidemiology

• Global users: amphetamine 30 mln+ (UNODC).
• Sex: higher in males.
• Comorbidity: psychosis, MDD, anxiety, cardiovascular, skin lesions (self-excoriation, ‘meth mouth’).

4. Aetiology and pathogenesis

• Heritability 40–50%.
• Neurobiological — release of dopamine and norepinephrine and blockade of their reuptake; severe neurotoxicity (especially methamphetamine — to dopamine neurons).

5. Clinical features

• Intoxication — euphoria, hypervigilance, mydriasis, tachycardia, hypertension, hyperthermia; in severe cases: paranoid psychosis, agitation, myocardial infarction, stroke, seizures, rhabdomyolysis.
• Withdrawal — “crash” — depressive mood, anhedonia, fatigue, hypersomnia, appetite, intense cravings; high suicide risk.
• Chronic use — psychosis (paranoid delusions, hallucinations), cognitive deficit, “meth mouth” (tooth decay), skin picking.
• MDMA (6C4C) — hyponatremia, hyperthermia, serotonin syndrome, neurotoxicity.

6. Diagnosis

6.1 Unified diagnostic criteria

DSM-5-TR 11 criteria (AUD structure). Unlike the single DSM-5-TR scale, ICD-11 uses three separate categories: episode of harmful use, harmful pattern of use, and dependence. ICD-11 duration requirement: harmful pattern of use — at least 12 months if use is episodic, at least 1 month if continuous; dependence — at least 12 months, or at least 3 months if use is continuous (daily or almost daily).

6.2 Source-specific clarifications

• SAMHSA TIP 33 — stimulant use.
• NIDA — methamphetamine research reports.

6.3 Diagnostic algorithm

1. Clinical interview.
2. Toxicology.
3. EKG, troponin.
4. Comorbidity (psychosis, MDD, cardiovascular).

6.4 Differential diagnosis

7. Examination and assessment

• Toxicology.
• EKG, troponin, CPK (rhabdomyolysis).
• Dental and skin examination.
• C-SSRS.

8. Treatment

1. Psychosocial — first line:
   • Contingency management;
   • CBT;
   • MI;
   • Matrix Model — manualized comprehensive program for amphetamine dependence.
2. Pharmacotherapy — No specific FDA-approved medication exists; off-label: mirtazapine, naltrexone + bupropion (Trivedi M.H. NEJM 2021 — ADAPT-2 trial combination for methamphetamine — modest effect).
3. Acute intoxication — benzodiazepine for agitation; antipsychotic in psychosis.
4. Comorbid psychosis — parallel treatment.

Source-specific specifications

• SAMHSA TIP 33.
• NIDA.
• Trivedi M.H. et al. NEJM 2021 — initial evidence base for naltrexone + bupropion in methamphetamine dependence.

Treatment methods

1. Matrix Model — 16-week structured program — CBT + family + 12-step + single physician. Evidence base for amphetamine/methamphetamine.
2. Contingency Management — Reward for negative test.
3. Naltrexone + Bupropion (ADAPT-2) — Primary RCT evidence in methamphetamine addiction; off-label.

9. Prognosis

• With multimodal approach, remission 30–50%.
• Comorbid psychosis indicates a poor prognosis.

10. Myths and misconceptions

Myth 1: “Methamphetamine is safer than ‘Spice’ or other ‘designer drugs’”

Evidence: Methamphetamine induces high neurotoxicity, psychosis, and mortality.

Myth 2: “MDMA is safe as a ‘pure’ substance”

Evidence: MDMA — hyperthermia, hyponatremia, serotonin syndrome; ‘pure’ substance is typically adulterated (synthetic cathinones, fentanyl).

Myth 3: “Detoxification is sufficient for stimulant dependence”

Evidence: Contingency management and CBT-based; sole detox leads to relapse >90%.

Myth 4: “Antidepressants cure stimulant addiction”

Evidence: single antidepressant ineffective; ADAPT-2 provides preliminary evidence for combination.

Myth 5: “Stimulant users are ‘productive’ and do not require intervention”

Evidence: Short-term performance boost illusion; long-term cognitive, psychiatric, cardiac complications.

11. Sources

1. WHO. ICD-11. 6C46 Disorders due to use of stimulants. 2024.
2. APA. DSM-5-TR. 2022.
3. SAMHSA. TIP 33. 2021.
4. NIDA. Methamphetamine Research Report. 2019.
5. Trivedi M.H. et al. Bupropion and Naltrexone in Methamphetamine Use Disorder. NEJM 2021;384(2):140–153.
6. Rawson R.A. et al. Matrix Model. SAMHSA.