Substance Use Disorders — Stimulants, Sedative-Hypnotics, and Cannabis
Clinical Snapshot
Substance use disorder (SUD) is a problematic pattern of substance use leading to clinically significant impairment or distress. The DSM-5-TR defines it with a single 11-criteria framework applied across substances: 2-3 criteria present within a 12-month period indicates a mild disorder, 4-5 a moderate disorder, and 6 or more a severe disorder.[1] This chapter applies that framework to the substance classes not already covered by this platform's dedicated Opioid-Related Disorders, Alcohol-Related Disorders, and Tobacco Use Disorder chapters: stimulants (cocaine and amphetamine-type stimulants — methamphetamine, amphetamine, and prescription stimulants), sedative-hypnotics (benzodiazepine use disorder specifically), and cannabis. Refer to those existing chapters for opioid, alcohol, and tobacco/nicotine content, none of which is repeated here.
These three substance classes behave very differently from one another, and from opioids and alcohol, and conflating them is a genuine and common source of clinical error. Stimulant withdrawal is primarily dysphoric and, while genuinely unpleasant and a real relapse risk, is not typically life-threatening on its own — acute stimulant intoxication, in contrast, carries a real cardiovascular emergency risk.[2] Benzodiazepine (sedative-hypnotic) withdrawal is closer to the inverse: it is genuinely dangerous, including a real seizure risk, which is why abrupt discontinuation after more than about 4 weeks of regular use should never be the default plan.[3] Cannabis use disorder has become increasingly clinically relevant as legalization has broadened access and normalized frequent use, and carries its own under-recognized complication, cannabinoid hyperemesis syndrome (see Recognize the Condition).[4] A theme running through this whole chapter: for both stimulant use disorder and cannabis use disorder, no medication is approved by Health Canada or the FDA, and structured psychosocial treatment is the primary, first-line therapy — pharmacotherapy is either absent, off-label, or narrowly symptom-targeted (see Choose Initial Treatment).[2][5] Rates of stimulant-related harm are rising quickly: overdose death rates have increased roughly threefold for cocaine and roughly twelvefold for other stimulants (methamphetamine, amphetamine, and prescription stimulants) over the past decade, driven in part by contamination of the stimulant supply with high-potency synthetic opioids such as fentanyl.[2]
Recognize the Condition
The DSM-5-TR substance use disorder framework — one model, applied across substances
The same 11 criteria apply whether the substance in question is a stimulant, a sedative-hypnotic, cannabis, or another substance: the substance taken in larger amounts or over a longer period than intended; a persistent desire or unsuccessful efforts to cut down or control use; a great deal of time spent obtaining, using, or recovering from the substance; craving, or a strong desire or urge to use; recurrent use resulting in a failure to fulfill major role obligations at work, school, or home; continued use despite persistent or recurrent social or interpersonal problems caused or worsened by use; important social, occupational, or recreational activities given up or reduced because of use; recurrent use in physically hazardous situations; continued use despite knowledge of a persistent or recurrent physical or psychological problem likely caused or worsened by the substance; tolerance (needing markedly more for the same effect, or a markedly reduced effect at the same amount); and withdrawal (a substance-specific withdrawal syndrome, or using the substance or a closely related one to relieve or avoid it).[1] As with any diagnostic framework, severity is not a judgment of the person — 2-3 criteria is mild, 4-5 is moderate, and 6 or more is severe.[1][3]
Stimulant intoxication
Look for hyperadrenergic signs: tachycardia, hypertension, agitation, diaphoresis, mydriasis, and hyperthermia, with psychosis possible in more severe presentations. Acute intoxication can produce several genuinely life-threatening complications, including acute coronary syndrome, myocardial infarction, hypertensive emergency, hyperthermia, and acidosis — these require immediate assessment and an appropriate level of care, not simply "riding it out."[2] Cocaine also has local anesthetic-like effects at cardiac sodium channels and can widen the QRS complex and impair contractility during severe intoxication.[2]
Stimulant withdrawal
Abrupt reduction or discontinuation after regular use typically produces 12-24 hours of somnolence and irritability, likely reflecting catecholamine depletion and sleep deprivation. This initial phase is followed by a genuinely important post-acute withdrawal period: depression, anxiety, insomnia, and paranoia that can persist for weeks to months and meaningfully increase the risk of decompensation and return to use if not actively assessed for and treated.[2] In contrast to benzodiazepine withdrawal below, this syndrome is not typically life-threatening on its own — but suicidality risk can genuinely increase specifically as intoxication wanes and acute withdrawal begins, and should be actively asked about.[2]
Benzodiazepine (sedative-hypnotic) use disorder
Physiologic dependence can develop relatively quickly with regular use — as many as 15% of regular users are dependent after 4 months, and about 50% after 2 years, with some sources citing even higher rates.[3] It is important to distinguish physiologic dependence, an expected pharmacological consequence of regular use of many sedative-hypnotics, from a true benzodiazepine use disorder, which requires meeting 2 or more of the same 11 DSM-5 criteria described above — not every physiologically dependent patient has a use disorder, and clinicians should not presume they do.[3]
Benzodiazepine (sedative-hypnotic) withdrawal
This is genuinely dangerous, unlike stimulant withdrawal above. Characteristic withdrawal features include autonomic hyperactivity, hand tremor, insomnia, nausea or vomiting, transient sensory hallucinations or illusions, psychomotor agitation, anxiety, and seizures.[3] This is precisely why abrupt discontinuation after more than about 4 weeks of regular use should never be the default plan (see Choose Initial Treatment).[3]
Cannabis use disorder and withdrawal
Cannabis use disorder is diagnosed using the same general 11-criteria framework above, applied to cannabis. A real, DSM-5-TR-recognized cannabis withdrawal syndrome can follow stopping or substantially reducing heavy, prolonged use, typically developing within about a week: irritability, anger, or aggression; nervousness or anxiety; sleep difficulty; decreased appetite or weight loss; restlessness; depressed mood; and at least one physical symptom causing significant discomfort, such as abdominal pain, tremor, sweating, fever, chills, or headache.[1]
Cannabinoid hyperemesis syndrome (CHS) — a genuinely important and under-recognized complication
CHS occurs in the setting of long-term, heavy (often daily) cannabis use and follows a characteristic 3-phase course.[4]
- Prodromal phase — lasting months. Morning nausea and abdominal discomfort, but the patient typically eats well, maintains weight, and remains functional. This is where the "cannabis paradox" drives the cycle: cannabis has real antiemetic properties at low doses, so patients continue or increase use believing it is relieving their nausea, unaware that chronic heavy use is what is causing it.[4]
- Hyperemetic phase — lasting days. Intense, persistent nausea and frequent vomiting, sometimes up to 5 times per hour, with sympathetic overactivity: tachycardia, hypertension, hot flashes, and sweating.[4]
- Recovery phase — ranging from weeks to months. Symptoms fully resolve and normal eating resumes, until a relapse if cannabis use is restarted.[4]
Compulsive hot-water bathing or showering for symptom relief is a classically described feature — proposed to work by stabilizing a thalamic thermostat disrupted by chronic cannabis use, though this mechanism has not been empirically validated — but it is not universal: more than 10% of patients with CHS do not exhibit it, and the same behaviour can occur in cannabis-unrelated cyclic vomiting syndrome. Its absence should not be used to rule CHS out.[4] CHS is frequently misdiagnosed or goes unrecognized for a long time, given inconsistent diagnostic criteria, subjective symptoms, and its strong resemblance to cyclic vomiting syndrome — patients often undergo extensive, unnecessary imaging and other workup (biliary studies, CT) across multiple presentations before the correct diagnosis is made.[4]
Risk Factors
- Co-occurring psychiatric conditions — depression, anxiety, ADHD, and trauma-related disorders are common across all three substance classes covered in this chapter and should be actively screened for and treated concurrently, not sequentially.[2]
- Stimulants — young adult age and untreated ADHD — nonmedical use of a prescription stimulant should specifically prompt evaluation for underlying ADHD, which may itself need treatment.[2]
- Stimulants — a contaminated, unregulated supply — stimulants obtained outside a pharmacy are increasingly combined with, or contaminated by, high-potency synthetic opioids such as fentanyl, which is a major driver of the sharp rise in stimulant-related overdose deaths described above and a key reason harm reduction applies here as much as it does to opioids.[2]
- Benzodiazepines — older age, female sex, dependent personality, and a current or previous substance use disorder — all identified risk factors for developing a benzodiazepine use disorder.[3]
- Benzodiazepines — higher dose and longer duration — a dose under 10 mg diazepam-equivalent/day is associated with a higher likelihood of successful tapering, and duration of use beyond 4 weeks is itself a marker of elevated risk.[3]
- Benzodiazepines — co-prescribing with opioids or alcohol — should generally be avoided; the combination substantially raises risk beyond either substance alone.[3]
- Cannabis — early age of initiation — starting before age 16 specifically is associated with a range of adverse health and social outcomes in young adult life, plausibly related to the impact of cannabis on a brain that is not done developing until the mid-20s.[6]
- Cannabis — frequency and intensity of use — daily or near-daily use is among the strongest and most consistent predictors of cannabis-related harm, including cannabis use disorder itself.[6]
- Cannabis — high-THC-content products or concentrates — associated with higher risk for both acute and chronic problem outcomes than lower-THC, higher-CBD products.[6]
- Cannabis — a personal predisposition to, or first-degree family history of, psychosis or another substance use disorder — this specific group is advised to abstain from cannabis altogether rather than aiming for lower-risk use.[6]
Red Flags & Refer
Any of the following changes the plan from routine counselling to immediate escalation:
- A stimulant-induced cardiovascular emergency — chest pain or suspected acute coronary syndrome, a hypertensive emergency, marked tachyarrhythmia, hyperthermia, or QRS widening — escalate to acute care immediately; begin treating the underlying intoxication (a GABAergic agent) even while arranging transfer.[2]
- Agitation or psychosis not responding to de-escalation and setting-level medication management — coordinate transition to a higher level of care rather than continuing to manage in place.[2]
- Any patient on a benzodiazepine or other sedative-hypnotic for more than about 4 weeks facing abrupt discontinuation — whether initiated by the patient, a hospitalization, incarceration, or a prescriber change — flag urgently for a taper plan or supervised medical withdrawal management given real seizure risk.[3]
- Escalating benzodiazepine use, a failed prior outpatient taper attempt, or significant psychopathology alongside a benzodiazepine use disorder — refer to a specialty addiction or mental health service rather than repeating the same outpatient approach.[3]
- Suspected cannabinoid hyperemesis syndrome with significant dehydration, electrolyte derangement, or diagnostic uncertainty — needs medical evaluation; once CHS is recognized in a patient with a prior confirmed episode, avoid reflexively repeating imaging or endoscopy already completed at earlier presentations.[4]
- Increasing suicidality — can genuinely increase specifically as stimulant or benzodiazepine intoxication wanes and withdrawal begins; ask directly rather than assuming a stable baseline.[2]
- Any patient obtaining stimulants from an unregulated or nonmedical source — real risk of fentanyl or other contamination; offer or prescribe naloxone and drug-checking information proactively rather than waiting for the patient to raise it.[2]
Assessment & Diagnosis
Diagnosis is clinical
Diagnosis of any substance use disorder covered in this chapter is made clinically against the DSM-5-TR 11-criteria framework above, supported by history, physical examination, and any available collateral information.[1] Toxicology testing can inform the differential diagnosis and identify substance use that could produce drug-drug interactions relevant to pharmacotherapy, but it should never replace clinical assessment — a negative screen does not rule out a novel psychoactive substance not captured by standard immunoassays.[2]
Investigations for stimulant use
In patients with long-term or heavy stimulant use, maintain an elevated degree of suspicion for cardiac and renal disorders, a lower threshold for ECG testing based on history and examination findings, and a lower threshold for creatine kinase testing when rhabdomyolysis is suspected.[2] When reviewing complete blood count results in a patient with cocaine use specifically, watch for neutropenia — levamisole, a common cocaine adulterant, can cause immunosuppression, in particular neutropenia, and small-vessel vasculitis, and unexplained neutropenia in a cocaine user should prompt consideration of this cause.[2]
Assessing benzodiazepine (sedative-hypnotic) use
A complete assessment establishes the original indication, current dose (a diazepam-equivalent conversion can be a useful common reference point), duration of use, features specifically indicative of a use disorder rather than simple physiologic dependence, readiness to change, and co-occurring medical and psychiatric comorbidities, including any other current or past substance use.[3] Multiple concurrent sedative-hypnotics are common and should be identified explicitly as part of this assessment — simplifying to a single agent is itself an early step in management, not something to defer.[3]
Assessing cannabis use and screening for cannabinoid hyperemesis syndrome
Assess frequency and intensity of use (daily or near-daily use specifically), product potency and THC content, and route of administration.[6] In any patient presenting with recurrent or cyclic vomiting who reports chronic, heavy cannabis use, actively consider cannabinoid hyperemesis syndrome in the differential rather than proceeding directly to repeat imaging or empiric antiemetics alone.[4]
Treatment Targets
- Recognize and manage acute, potentially life-threatening complications first — a stimulant-induced cardiovascular emergency or a benzodiazepine withdrawal seizure — before addressing longer-term substance use treatment.
- For benzodiazepine (sedative-hypnotic) use disorder, achieve a safe, supervised, gradual taper rather than abrupt discontinuation, minimizing withdrawal symptoms, rebound, and relapse risk.
- For stimulant use disorder, engage the patient in structured psychosocial treatment — contingency management foremost — as the primary, evidence-based intervention.
- For cannabis use disorder, reduce frequency and intensity of use, or achieve full abstinence where cannabinoid hyperemesis syndrome or another significant harm is present, through psychosocial treatment.
- Identify and treat co-occurring psychiatric conditions (depression, anxiety, ADHD, trauma-related disorders) concurrently, not sequentially.
- Reduce overdose and infectious-disease risk through harm reduction: naloxone access for anyone using stimulants from an unregulated supply, drug-checking awareness, and safer-use counselling.
- Set and reinforce realistic expectations directly with patients: no medication is approved for stimulant use disorder or cannabis use disorder, and pharmacotherapy plays a narrow, adjunctive, or acute-symptom role throughout this entire chapter.
- Avoid iatrogenic harm — a reflexive antipsychotic choice that lowers seizure threshold, an abruptly discontinued sedative-hypnotic, or a missed cannabinoid hyperemesis syndrome diagnosis leading to repeated unnecessary investigations.
Choose Initial Treatment
Stimulant use disorder — psychosocial treatment first; no approved medication
1st line, every patient contingency management (CM) — structured, tangible incentives for objectively verified abstinence — has the strongest and most consistent evidence of any intervention studied for stimulant use disorder and is now considered the standard of care; combine it with another psychosocial treatment rather than using it alone.[2][7] Cognitive behavioural therapy (CBT), the community reinforcement approach (CRA), and the Matrix Model are the next-best-supported additions alongside CM (see Non-Pharmacologic Treatment).[2] No medication is approved by Health Canada or the FDA to treat stimulant use disorder itself — every pharmacologic option below is an off-label trial, generally reserved for patients not achieving their goals with psychosocial treatment alone.[2]
Off-label pharmacotherapy for stimulant use disorder
Cocaine use disorder clinicians can consider bupropion to promote abstinence — low-certainty evidence, with additional consideration for patients with co-occurring tobacco use disorder or depression, since bupropion can also treat both.[2] Topiramate is a reasonable alternative, with additional consideration when alcohol use disorder also co-occurs.[2]
Amphetamine-type stimulant use disorder, low-to-moderate-frequency use (under 18 days/month) bupropion alone is a reasonable option.[2] Moderate-to-severe use the combination of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg daily) has moderate-certainty evidence — the ADAPT-2 trial found a modest but statistically significant treatment effect (13.6% vs 2.5% response with placebo, an 11.1-percentage-point difference), with additional consideration for co-occurring alcohol use disorder, tobacco use disorder, or depression.[8][2] Topiramate and mirtazapine are also reasonable off-label alternatives, both with low-certainty evidence.[2]
Avoid prescribing a psychostimulant medication for stimulant use disorder itself outside of a genuine, confirmed co-occurring ADHD indication, and manage that indication by, or in close consultation with, a clinician experienced in addiction medicine or addiction psychiatry given the controlled-substance and diversion risk.[2]
Managing acute stimulant intoxication, agitation, and the hyperadrenergic state
Agitation, delirium, or a hyperadrenergic state use verbal and nonverbal de-escalation first, but do not let it delay medication in a patient at imminent risk of severe complications — benzodiazepines can be considered first-line pharmacologic treatment for both agitation/confusion and the hyperadrenergic state itself.[2] Stimulant-induced psychotic symptoms treat with an antipsychotic, with urgency, formulation, and duration guided by etiology and severity.[2] Avoid chlorpromazine and clozapine for stimulant-induced psychosis specifically — both lower seizure threshold in a population already at elevated seizure risk.[2]
Hypertensive emergency use short-acting agents (a dihydropyridine calcium channel blocker or phentolamine) rather than a long-acting antihypertensive, which risks abrupt hemodynamic collapse once the stimulant effect wanes; add nitroglycerin specifically if there are signs of cardiac ischemia.[2] Avoid an unopposed beta blocker in acute stimulant intoxication; if a beta blocker is used, choose one with concomitant alpha-1 antagonism (e.g., labetalol or carvedilol), and if an unopposed beta blocker has already been given, pair it with a coronary vasodilator.[2] QRS widening treat with sodium bicarbonate, which improves both the conduction block/contractility from cocaine's local-anesthetic sodium-channel effect and any concurrent metabolic acidosis.[2] Seizures well explained by stimulant intoxication or withdrawal treat with benzodiazepines; if refractory, phenobarbital or propofol.[2]
Benzodiazepine (sedative-hypnotic) use disorder — never abrupt discontinuation
Abrupt discontinuation of a benzodiazepine or other sedative-hypnotic after more than about 4 weeks of regular use should never be the plan — real risk of withdrawal seizures, rebound symptoms, and a substantially higher likelihood of relapse to use.[3]
Mainstay approach a person-centred, stepped-care gradual dose reduction, planned and shared with the patient — agreeing on the reduction schedule, optimizing treatment of whatever underlying condition (insomnia, anxiety) originally drove use, developing a plan for emergent withdrawal or rebound symptoms, and scheduling regular follow-up visits to review progress.[3] Cognitive behavioural therapy delivered alongside the taper improves the patient's experience of the process and the likelihood of stopping successfully.[3] General addiction-medicine practice for a use disorder often converts a short-acting or high-potency agent to a longer-acting equivalent (commonly diazepam) specifically to smooth the taper and reduce peak-trough symptom fluctuation; dedicated Canadian guidance for older adults, however, finds that routine switching from a short- to a long-half-life agent is not generally recommended in that specific population, reserving it for particular situations such as alprazolam dependence or a limited number of available pill strengths — apply routine substitution selectively, on its own merits, rather than as an automatic default.[3] Multiple concurrent sedative-hypnotics simplify to a single agent as an explicit taper-plan step, not something left unaddressed.[3] Avoid substituting an unrelated drug class specifically to blunt withdrawal symptoms during a gradual taper — this is not routinely recommended and does not substitute for a properly paced dose reduction.[3]
Acute withdrawal management monitor with a validated tool (for example, the Clinical Institute Withdrawal Assessment for Benzodiazepines [CIWA-B] or the Benzodiazepine Withdrawal Symptom Questionnaire) and manage with judicious, symptom-driven dosing of an appropriate benzodiazepine.[3] Escalating use, a failed prior taper, high relapse risk, or significant psychopathology refer to a specialty addiction or mental health service rather than repeating the same outpatient approach.[3]
Cannabis use disorder and cannabinoid hyperemesis syndrome
1st line, cannabis use disorder structured psychosocial treatment — motivational interviewing/brief intervention plus CBT. There are currently no pharmacotherapies approved for cannabis use disorder, and a 2019 Cochrane review of 21 randomized trials found incomplete, low-to-very-low-certainty evidence for every medication studied (including SSRIs, bupropion, buspirone, and atomoxetine); THC preparations showed some reduction in withdrawal symptom intensity but no higher abstinence rate than placebo and remain experimental, not a recommended treatment.[5] For patients not ready to stop entirely, discuss the Lower-Risk Cannabis Use Guidelines directly: avoid daily or near-daily use, choose lower-THC/higher-CBD products, avoid deep inhalation and breath-holding, and never drive within at least 6 hours of use.[6]
Cannabinoid hyperemesis syndrome, acute episode supportive care (IV fluids, electrolyte correction) plus symptomatic treatment: topical capsaicin cream (0.025-0.15%) applied to the abdomen has real trial evidence for reducing acute nausea and shortening emergency department stays; haloperidol has outperformed ondansetron for nausea and vomiting in trial data (monitor QTc); droperidol has also shown benefit over placebo; IV lorazepam can help via its GABA-agonist, anxiolytic-adjacent effect.[4] Definitive treatment complete cessation of cannabis in any form is required for full, lasting resolution — this is the only curative intervention. Full recovery can take anywhere from a few months to as long as about 4 years of confirmed abstinence, and low-dose amitriptyline can help support the abstinence period and reduce recurrence.[4]
Harm reduction across all three substance classes
For any patient using stimulants obtained from an unregulated or nonmedical source, or who is socially connected to others who do, prescribe or distribute naloxone, or refer to a community source, given the real risk of fentanyl or other opioid contamination in the stimulant supply — do not wait for the patient to raise it first.[2] Recommend comprehensive drug checking, including fentanyl test strips, each time a new supply is obtained from a nonmedical source, and review technique with the patient.[2] Refer to a supervised consumption site where one is available; in the Canadian context specifically, drug-checking services and supervised consumption sites operate in a number of jurisdictions as part of the broader harm-reduction landscape and are a reasonable referral alongside pharmacy-based counselling.[2]
Non-Pharmacologic Treatment
Contingency management (CM)
An operant-conditioning-based intervention: tangible reinforcers (vouchers, prizes, or similar incentives) contingent on objectively verified abstinence, typically a negative urine drug screen, often escalating in value with sustained abstinence. It has demonstrated the best effectiveness of any intervention studied for stimulant use disorder across dozens of randomized trials and is considered the current standard of care, generally delivered alongside another psychosocial treatment rather than alone.[2] A network meta-analysis of 50 randomized trials (about 6,900 participants total) across 12 psychosocial interventions for cocaine and amphetamine addiction found that CM combined specifically with the community reinforcement approach (CRA) was the only combination that meaningfully increased the number of patients achieving abstinence compared with usual care, with fewer dropouts as well.[7]
Cognitive behavioural therapy (CBT), community reinforcement approach (CRA), and the Matrix Model
CBT teaches recognition of, and coping strategies for, cravings and triggers, and has the most consistent evidence after CM. CRA uses community, family, and lifestyle-based reinforcers to support a substance-free lifestyle more broadly. The Matrix Model is a structured, manualized intensive outpatient program combining individual counselling, family education, social support, and relapse-prevention skills, developed specifically for stimulant use disorder. All three are reasonable additions alongside CM, or reasonable alternatives where CM access is genuinely limited.[2]
Motivational interviewing and brief intervention
For any patient who screens positive for risky stimulant or cannabis use, a brief motivational-interviewing-based intervention is a reasonable first step to encourage reduction or cessation, with a warm-handoff referral for comprehensive assessment and treatment for those who screen positive for a likely use disorder.[2][6]
Cognitive behavioural therapy during a benzodiazepine taper
Adding CBT during a gradual benzodiazepine or other sedative-hypnotic taper improves the patient's tolerance of the process and increases the likelihood of successfully stopping — offer it alongside, not instead of, the taper plan itself.[3]
Patient education — harm reduction across substances
- Explain plainly that no medication is approved for stimulant use disorder or cannabis use disorder, and that structured psychosocial treatment — contingency management especially, for stimulants — is genuinely the most effective option available. This reframes a referral as active, evidence-based treatment rather than a fallback.
- For any patient using stimulants from an unregulated source, offer naloxone and drug-checking information as routine harm-reduction counselling, not only after a close call.[2]
- For cannabis, counsel on the Lower-Risk Cannabis Use Guidelines directly: avoid daily or near-daily use, choose lower-THC products, avoid deep inhalation and the Valsalva manoeuvre, and wait at least 6 hours after use before driving or operating machinery — longer depending on the individual and the specific product used.[6]
- For anyone with a personal or first-degree family history of psychosis or a substance use disorder, counsel that current evidence supports avoiding cannabis use altogether given a substantially higher risk profile in this specific group.[6]
- For a patient with confirmed or suspected cannabinoid hyperemesis syndrome, explain the "cannabis paradox" directly — that continuing to use cannabis to relieve the nausea is exactly what perpetuates the cycle, since patients typically continue use during the prodromal phase believing it is helping.[4]
- For a patient starting a benzodiazepine taper, explain the rationale (real long-term harm from continued use, including cognitive impairment and fall risk) and involve them directly in building the schedule — patients engage more readily with a gradual dose-reduction plan once they understand why, not just what.[3]
Special Populations
Pregnancy
Stimulant intoxication and withdrawal in pregnancy should generally be managed the same as in any other patient, including standard fetal well-being assessment — concern for fetal well-being should never be prioritized over the pregnant patient's own health, and untreated intoxication or withdrawal, including the resulting risk of return to stimulant use, poses its own direct risk to the fetus.[2] Methamphetamine-induced hypertension can be genuinely difficult to distinguish from gestational hypertension; manage hypertension in pregnancy and postpartum per standard obstetric practice, typically labetalol or nifedipine, with magnesium for seizure prophylaxis where indicated.[2] Provide additional treatment support specifically around the time of birth — the postpartum period carries increased stress and a real risk of return to stimulant use.[2] For cannabis, current Canadian guidance specifically advises this group to abstain altogether, given evidence of adverse maternal and neonatal outcomes including low birth weight and growth reduction.[6]
Breastfeeding
Educate patients who use stimulants about the risks of use while breastfeeding, and counsel against breastfeeding while actively using stimulants outside of a prescribed indication.[2]
Adolescents and young adults
Provide the same treatment, harm reduction, and recovery support services as adults, delivered in a developmentally responsive manner — a younger patient does not need, or deserve, a fundamentally different or lesser standard of care.[2] For cannabis specifically, initiating use before age 16 is associated with a substantially higher risk of adverse health and social outcomes later in young adult life, plausibly related to the impact of cannabis on a brain that is not done developing until the mid-20s — for those who will use regardless, deferring the age of first use is itself a genuine harm-reduction message.[6]
Older adults
Older adults have increased sensitivity to benzodiazepines and other sedative-hypnotics and a decreased ability to metabolize some longer-acting agents such as diazepam. Long-term use in this population is specifically linked to a higher risk of cognitive impairment, delirium, falls, fractures, hospitalization, and motor vehicle crashes, and use beyond about 4 weeks should be avoided for most indications.[3] Routine switching to a long-half-life agent to ease tapering is not generally recommended specifically in this population, in contrast to broader addiction-medicine practice for a use disorder (see Choose Initial Treatment).[3]
Patients with co-occurring ADHD
Evidence supports pharmacotherapy, including psychostimulant medication, to treat a confirmed co-occurring ADHD diagnosis in a patient with stimulant use disorder — this is a distinct, legitimate indication from treating the stimulant use disorder itself, and should be managed by, or in close consultation with, a clinician experienced in addiction medicine or addiction psychiatry given the controlled-substance and diversion risk.[2] Any patient using a prescription stimulant nonmedically should be evaluated for underlying ADHD, which may itself need treatment.[2]
Renal and hepatic impairment
Dose-adjust topiramate for reduced renal function; use naltrexone with caution and baseline/periodic liver function testing in hepatic impairment given its own hepatotoxicity potential; reduce the bupropion dose and titrate more slowly in hepatic impairment given a lower seizure threshold at higher exposure. Confirm specifics against each drug's own Drug Database entry or current product monograph.
Monitoring & Follow-Up
- For anyone with long-term or heavy stimulant use, maintain ongoing clinical vigilance for cardiac and renal complications even outside of an acute presentation, with a lower threshold for ECG or targeted lab testing based on new symptoms.[2]
- Monitor specifically for suicidality as stimulant or benzodiazepine intoxication wanes and acute withdrawal begins — this is a recognized higher-risk window, not simply a background risk level.[2]
- Track post-acute stimulant withdrawal symptoms (depression, anxiety, insomnia, paranoia) proactively for weeks to months after the acute phase resolves — these are expected, treatable, and a real relapse risk if missed, not automatically a new or separate psychiatric diagnosis.[2]
- For a benzodiazepine taper, schedule regular visits specifically to review progress, adjust the pace of dose reduction, and manage emergent withdrawal or rebound symptoms — a taper plan handed to a patient without follow-up is incomplete.[3]
- Provide additional support and closer follow-up around the postpartum period specifically for patients with stimulant use disorder, given the elevated relapse risk in that window.[2]
- For a patient recovering from cannabinoid hyperemesis syndrome, confirm sustained cannabis abstinence at follow-up rather than assuming the acute episode resolving means the underlying driver has been addressed — recurrence with resumed use is expected, and full recovery of the cycle can take months to years.[4]
- Reassess any off-label pharmacotherapy for stimulant use disorder against its specific target (abstinence, reduced-use days) at a defined interval, and stop it if it is not clearly helping rather than continuing indefinitely.[2]
Common Errors to Avoid
- Assuming any medication is approved by Health Canada or the FDA for stimulant use disorder or cannabis use disorder — none is; every pharmacologic option in this chapter for those two conditions is off-label, adjunctive, or acute-symptom management only.
- Abruptly discontinuing a benzodiazepine or other sedative-hypnotic after more than about 4 weeks of regular use — real seizure and rebound risk; always plan a gradual, supervised taper instead.
- Using an unopposed beta blocker, or chlorpromazine/clozapine, in acute stimulant intoxication or stimulant-induced psychosis.
- Missing cannabinoid hyperemesis syndrome in a chronic daily cannabis user with cyclic vomiting, and instead pursuing repeated unnecessary imaging or endoscopy across multiple presentations.
- Assuming the absence of compulsive hot-water bathing rules out cannabinoid hyperemesis syndrome — it is a classic but not universal feature.
- Confusing physiologic dependence, an expected consequence of regular use of many sedative-hypnotics, with a true substance use disorder — the two are not the same, and not every dependent patient meets criteria for a use disorder.
- Delaying or replacing psychosocial treatment with medication for stimulant use disorder or cannabis use disorder, rather than using medication, where evidence supports it at all, as an adjunct.
- Not offering naloxone or drug-checking information to a patient using stimulants from an unregulated supply, given the real risk of fentanyl or other contamination.
- Substituting an unrelated drug class specifically to blunt benzodiazepine withdrawal symptoms during a taper, rather than pacing the dose reduction itself appropriately.
- Treating new mood or anxiety symptoms during the expected post-acute stimulant withdrawal window as a separate psychiatric diagnosis before allowing the weeks-to-months window to run its course.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
No medication is approved by Health Canada or the FDA for stimulant use disorder or cannabis use disorder themselves. Every stimulant- and cannabis-related row below is an off-label trial, an acute-symptom treatment, or a harm-reduction agent — not a curative or approved therapy. Select any drug name to open its complete Pharmasist Drug Database page.
Off-Label Pharmacotherapy for Stimulant Use Disorder
Reserved for patients not achieving their goals with contingency management and another psychosocial treatment alone; every agent here has low-to-moderate-certainty trial evidence only.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Bupropion (extended-release) | Dosing: 150-300 mg PO once daily, per product monograph | Seizure risk (dose-related), insomnia, dry mouth, headache | Numerous CYP2D6 interactions; avoid with an MAOI or another bupropion-containing product | For cocaine use disorder, or low-to-moderate-frequency (under 18 days/month) amphetamine-type stimulant use disorder; extra benefit if tobacco use disorder or depression also co-occur. |
| Naltrexone (extended-release injectable) + bupropion | Naltrexone: 380 mg IM every 3 weeks Bupropion: 450 mg PO once daily (extended-release) | Naltrexone: injection-site reaction, nausea, headache. Bupropion: seizure risk, insomnia | Naltrexone can precipitate withdrawal in a patient with recent opioid use — confirm opioid-free status first | For moderate-to-severe amphetamine-type stimulant use disorder (ADAPT-2 protocol); modest but statistically significant benefit over placebo (13.6% vs 2.5% treatment response). |
| Topiramate | Titration: Per product monograph, starting low and increasing gradually | Cognitive slowing/word-finding difficulty, paresthesias, weight loss, nephrolithiasis risk | May reduce the efficacy of estrogen-containing contraceptives at higher doses | For cocaine or amphetamine-type stimulant use disorder; extra consideration if alcohol use disorder co-occurs. |
| Mirtazapine | Dosing: 15-30 mg PO at bedtime, per product monograph | Sedation, weight gain, increased appetite | Additive sedation with other CNS depressants | For amphetamine-type stimulant use disorder; low-certainty evidence. |
Managing Acute Stimulant Intoxication, Agitation, and the Hyperadrenergic State
Benzodiazepines are first-line for both agitation and the hyperadrenergic state; add other agents only if the hyperadrenergic state persists despite an adequate GABAergic response.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Lorazepam | Dosing: 1-2 mg IV/IM/PO, repeated per response and product monograph | Sedation, respiratory depression at high doses | Additive CNS depression with other sedatives or alcohol | First-line for stimulant-induced agitation, confusion, and hyperadrenergic symptoms. |
| Diazepam | Dosing: 5-10 mg IV/PO, repeated per response and product monograph | Sedation, respiratory depression at high doses | Additive CNS depression with other sedatives or alcohol | An alternative GABAergic agent for agitation or hyperadrenergic symptoms. |
| Phenobarbital | Dosing: Per product monograph and local protocol | Sedation, respiratory depression | Additive CNS depression with other sedatives; numerous CYP interactions | Reserve for agitation or seizures refractory to benzodiazepines. |
| Propofol | Dosing: Per product monograph and local protocol, in a monitored setting | Hypotension, respiratory depression, injection-site pain | Additive CNS/respiratory depression with other sedatives | Reserve for severe, refractory agitation or seizures requiring airway management and continuous monitoring. |
| Labetalol | Dosing: Per product monograph and local protocol | Hypotension, bradycardia, bronchospasm | Additive hypotension with other antihypertensives | Combined alpha-1/beta antagonism avoids the unopposed-beta-blockade risk of a pure beta blocker in stimulant intoxication. |
| Carvedilol | Dosing: Per product monograph | Hypotension, bradycardia, dizziness | Additive hypotension with other antihypertensives | An alternative combined alpha-1/beta antagonist for the same reason as labetalol. |
| Nifedipine | Dosing: Per product monograph and local protocol | Hypotension, headache, flushing, reflex tachycardia | Additive hypotension with other antihypertensives | A short-acting dihydropyridine calcium channel blocker for a stimulant-associated hypertensive emergency. |
| Phentolamine | Dosing: Per product monograph and local protocol | Hypotension, reflex tachycardia, flushing | Additive hypotension with other antihypertensives | A short-acting alpha antagonist alternative for a stimulant-associated hypertensive emergency. |
| Nitroglycerin | Dosing: Per product monograph and local protocol | Headache, hypotension, reflex tachycardia | Contraindicated with a phosphodiesterase-5 inhibitor | Add specifically if there are signs or symptoms of cardiac ischemia during stimulant-associated chest pain or hypertensive emergency. |
| Sodium bicarbonate | Dosing: Per product monograph and local protocol | Metabolic alkalosis, hypernatremia, hypokalemia | None significant at standard emergency doses | For QRS widening from cocaine's local-anesthetic sodium-channel-blocking effect during severe intoxication; also corrects concurrent metabolic acidosis. |
Stimulant-Induced Psychosis
Urgency, formulation, and duration should be guided by severity and setting; avoid chlorpromazine and clozapine specifically, which lower seizure threshold in a population already at elevated risk.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Haloperidol | Dosing: Per product monograph and local protocol | Extrapyramidal symptoms, QTc prolongation, akathisia | Additive QTc effects with other QTc-prolonging drugs | A reasonable first choice for acute stimulant-induced psychosis. |
| Olanzapine | Dosing: Per product monograph and local protocol | Sedation, weight gain (with regular use), hypotension | Additive sedation with other CNS depressants | A reasonable atypical antipsychotic alternative for acute stimulant-induced psychosis. |
| Risperidone | Dosing: Per product monograph and local protocol | Extrapyramidal symptoms (dose-related), hypotension | Additive QTc effects with other QTc-prolonging drugs | Another reasonable atypical antipsychotic alternative. |
| Chlorpromazine | Stimulant-induced psychosis: Not recommended | Seizure risk, sedation, hypotension, QTc prolongation | Lowers seizure threshold; additive effects with other QTc-prolonging drugs | Avoid specifically for stimulant-induced psychosis given seizure-threshold-lowering risk in an already seizure-prone population. |
| Clozapine | Stimulant-induced psychosis: Not recommended | Seizure risk (dose-related), agranulocytosis, myocarditis, sedation | Lowers seizure threshold; numerous CYP interactions | Avoid specifically for stimulant-induced psychosis given seizure-threshold-lowering risk; also not appropriate for acute, unstabilized presentations given its own monitoring requirements. |
Benzodiazepine (Sedative-Hypnotic) Use Disorder — Gradual Taper
Abrupt discontinuation after more than about 4 weeks of regular use is never the plan. A gradual, person-centred dose reduction is the mainstay; converting a short-acting or high-potency agent to a longer-acting equivalent can smooth the taper in general addiction-medicine practice, though dedicated Canadian guidance for older adults specifically finds routine switching is not generally needed in that population.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Diazepam | Taper: Gradual dose reduction per an individualized, shared schedule — no fixed universal rate | Sedation, cognitive impairment, ataxia (dose-related, more pronounced in older adults) | Additive CNS depression with alcohol, opioids, or other sedatives | Long half-life makes it a common taper anchor when converting from a shorter-acting or higher-potency agent. |
| Lorazepam | Taper: Gradual dose reduction per an individualized, shared schedule | Sedation, cognitive impairment, ataxia | Additive CNS depression with alcohol, opioids, or other sedatives | A common agent being tapered directly, particularly when converting to diazepam is not preferred. |
| Oxazepam | Taper: Gradual dose reduction per an individualized, shared schedule | Sedation, cognitive impairment, ataxia | Fewer active metabolites than diazepam; additive CNS depression with other sedatives | A shorter-acting agent sometimes preferred in significant hepatic impairment given simpler metabolism. |
| Temazepam | Taper: Gradual dose reduction per an individualized, shared schedule | Sedation, cognitive impairment, ataxia | Additive CNS depression with other sedatives | An intermediate-acting agent commonly being tapered when the original indication was insomnia. |
| Alprazolam | Taper: Gradual dose reduction per an individualized, shared schedule; conversion to a longer-acting agent may have a role here specifically | Sedation, marked rebound anxiety between doses, ataxia | Additive CNS depression with other sedatives | Its short half-life and high potency make withdrawal and rebound symptoms more prominent — one of the specific situations where converting to a longer-acting agent has a real role. |
Cannabinoid Hyperemesis Syndrome — Acute Symptomatic Treatment
Adjuncts to supportive care (IV fluids, electrolyte correction) during an acute episode. None of these treat the underlying disorder — complete cannabis cessation is the only definitive, curative treatment.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Capsaicin (topical) | Dosing: Applied topically to the abdomen per product labelling | Local burning/skin irritation at the application site | None significant | Applied to the abdomen (0.025-0.15% concentration); reduces acute nausea and shortens emergency department stays in trial data. |
| Haloperidol | Dosing: Per product monograph and local protocol | Extrapyramidal symptoms, QTc prolongation, akathisia | Additive QTc effects with other QTc-prolonging drugs | Outperformed ondansetron for nausea and vomiting in cannabinoid hyperemesis syndrome trial data; monitor QTc. |
| Lorazepam | Dosing: 1-2 mg IV every 4-6 hours, per product monograph and local protocol | Sedation | Additive CNS depression with other sedatives | IV dosing can provide symptomatic relief via its GABA-agonist, anxiolytic-adjacent effect. |
| Amitriptyline | Dosing: Low dose per product monograph, titrated as tolerated | Anticholinergic effects, sedation, QTc prolongation | Additive QTc effects with other QTc-prolonging drugs; caution with other serotonergic agents | Low-dose use during the recovery/abstinence period can help support sustained cannabis cessation and reduce recurrence. |
Harm Reduction
Applicable to anyone using stimulants, or any substance, from an unregulated or nonmedical source, given the real risk of fentanyl or other contamination.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Naloxone | Dosing: Per product monograph and local take-home naloxone program protocol | None with correct use; can precipitate withdrawal in an opioid-dependent patient | None significant | Prescribe, distribute, or refer to a community source proactively — do not wait for the patient to ask. |
References
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) — American Psychiatric Association. Washington (DC): American Psychiatric Publishing; 2022
- The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder — American Society of Addiction Medicine (ASAM) and American Academy of Addiction Psychiatry (AAAP) (Batki S, Ciccarone D, Hadland SE, et al.). ASAM/AAAP Clinical Practice Guideline, 2024
- Canadian Guidelines on Benzodiazepine Receptor Agonist Use Disorder Among Older Adults — Canadian Coalition for Seniors' Mental Health (CCSMH) / Canadian Academy of Geriatric Psychiatry. CCSMH, Toronto, Canada (2019)
- A Comprehensive Review and Update on Cannabis Hyperemesis Syndrome — Pharmaceuticals (Loganathan P, Gajendran M, Goyal H). Pharmaceuticals 2024;17(11):1549
- Pharmacotherapies for cannabis dependence — Cochrane Database of Systematic Reviews (Nielsen S, Gowing L, Sabioni P, Le Foll B). Cochrane Database Syst Rev 2019;1:CD008940
- Lower-Risk Cannabis Use Guidelines (LRCUG): An Evidence-Based Update — American Journal of Public Health (Fischer B, Russell C, Sabioni P, van den Brink W, Le Foll B, Hall W, Rehm J, Room R). Am J Public Health 2017;107(8):e1-e12
- Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis — PLoS Medicine (De Crescenzo F, Ciabattini M, D'Alò GL, et al.). PLoS Med 2018;15(12):e1002715
- Bupropion and Naltrexone in Methamphetamine Use Disorder — New England Journal of Medicine (Trivedi MH, Walker R, Ling W, et al.). N Engl J Med 2021;384(2):140-153
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.