Ganja

01Pathophysiology

Cannabis exerts its psychoactive effects primarily through delta-9-tetrahydrocannabinol (THC), which acts as a partial agonist at CB1 cannabinoid receptors. These receptors are densely distributed in the hippocampus, cerebral cortex, basal ganglia, and cerebellum, which directly explains the clinical profile of intoxication.

Activation of CB1 receptors in the hippocampus impairs short-term memory and learning. In the cerebellum and basal ganglia, CB1 stimulation leads to impaired motor coordination and slowed reaction time. Cortical CB1 activation produces the characteristic euphoria, altered time perception, and at higher doses, paranoia or frank psychosis. The hypothalamic effects drive increased appetite ("munchies") by stimulating orexigenic pathways. Tachycardia results from sympathetic activation and decreased parasympathetic tone, not from direct cardiac stimulation.

The conjunctival injection (red eyes), the single most recognizable physical exam finding, is caused by vasodilation of conjunctival blood vessels mediated through CB1 receptor activation.

With chronic, heavy use, the brain downregulates and desensitizes CB1 receptors as a compensatory adaptation. When cannabis is abruptly discontinued, the sudden loss of exogenous cannabinoid signaling in a system with reduced receptor sensitivity produces a withdrawal syndrome. This withdrawal is real and recognized in the DSM-5, though it is not life-threatening and does not produce seizures or delirium tremens, unlike alcohol or benzodiazepine withdrawal. The irritability, insomnia, and appetite loss of withdrawal are essentially the mirror image of the intoxication effects (euphoria becomes dysphoria, increased appetite becomes anorexia, sedation becomes insomnia).

A related and highly testable condition is cannabinoid hyperemesis syndrome (CHS), seen in long-term heavy users. CHS presents with cyclical nausea, vomiting, and abdominal pain paradoxically relieved by hot showers or baths. The pathophysiology is not fully understood but is thought to involve dysregulation of the endocannabinoid system in the gut and hypothalamus with chronic CB1 overstimulation.

02Classification and Clinical Manifestation

Cannabis Intoxication

Cannabis Withdrawal

Cannabinoid Hyperemesis Syndrome (CHS)

03Diagnostic Workup

The diagnostic approach to cannabis intoxication begins with clinical recognition. The combination of euphoria, conjunctival injection, increased appetite, and tachycardia in a young patient should immediately raise suspicion. A urine drug screen is the best initial confirmatory step and is widely available.

However, a critical testing pearl is the prolonged detection window of THC-COOH in urine. Because THC is highly lipophilic, it accumulates in fat tissue and is slowly released. A positive urine screen in a chronic user does not confirm acute intoxication; it only confirms use within a broad time window. If timing of use matters (e.g., emergency department presentation, altered mental status workup), a serum THC level is more informative because it reflects recent exposure.

Cannabis withdrawal requires no laboratory testing for diagnosis. It is diagnosed clinically using DSM-5 criteria: cessation after heavy prolonged use, followed by at least three characteristic symptoms (irritability, insomnia, decreased appetite, restlessness, depressed mood, or physical symptoms like tremor and diaphoresis) within approximately one week. The key diagnostic task on the exam is recognizing the clinical pattern and distinguishing it from other withdrawal syndromes.

For cannabinoid hyperemesis syndrome, diagnosis is clinical and requires the triad of chronic heavy cannabis use, cyclical vomiting, and relief with hot bathing. Workup is primarily aimed at excluding other diagnoses (e.g., cyclic vomiting syndrome, gastroparesis, small bowel obstruction). Imaging and labs are typically unremarkable aside from signs of dehydration.

04Management and Treatment

Acute intoxication is nearly always self-limited and requires only supportive care. Place the patient in a calm, quiet environment and provide verbal reassurance. Monitor heart rate (expect tachycardia) and observe for resolution. For patients with severe anxiety, panic attacks, or agitation, benzodiazepines are the treatment of choice: lorazepam 1 to 2 mg IV or IM, repeated every 15 to 20 minutes as needed.

If the patient presents with acute psychosis (hallucinations, severe paranoia, disorganized behavior), particularly after high-dose ingestion or use of edibles, benzodiazepines should be tried first. If psychotic symptoms persist, a low-dose antipsychotic such as haloperidol 5 mg IM may be added. It is important to note that there is no antidote for cannabis intoxication (unlike naloxone for opioids or flumazenil for benzodiazepines).

Cannabis withdrawal management is entirely supportive. There is no validated pharmacological protocol. Insomnia can be addressed with short courses of sleep aids (e.g., trazodone 50 to 100 mg at bedtime). Headache and myalgias respond to NSAIDs. Anxiety and irritability can be managed with brief reassurance and, if necessary, short-term anxiolytics. The patient should be counseled that symptoms are self-limited and will resolve within 1 to 2 weeks.

For cannabinoid hyperemesis syndrome, a high-yield exam pearl is that standard antiemetics (ondansetron, metoclopramide) are often ineffective. The best acute intervention is topical capsaicin cream (0.075%) applied to the periumbilical abdomen, which activates TRPV1 receptors and provides symptom relief. Intravenous fluids for rehydration and electrolyte correction are essential. The only definitive cure is complete cessation of cannabis use.

Long-term treatment of cannabis use disorder relies on behavioral therapies. CBT helps patients identify triggers and develop coping strategies. Motivational enhancement therapy addresses ambivalence about quitting. Contingency management uses incentive-based reinforcement for negative drug screens. There is currently no FDA-approved medication for cannabis use disorder, which is itself a testable fact.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on cannabis questions is by underestimating the clinical significance of withdrawal. Many students still believe cannabis withdrawal does not exist or is not clinically meaningful. It is a recognized DSM-5 diagnosis and can appear on the exam as a patient who is irritable, cannot sleep, has lost appetite, and recently stopped using marijuana after years of daily use. Recognizing this pattern is the core competency being tested.

A second frequent trap involves cannabinoid hyperemesis syndrome. The vignette will describe a young chronic cannabis user with recurrent vomiting and abdominal pain who has had multiple emergency visits and negative workups. The "hot shower relief" clue is pathognomonic, but some vignettes omit it and instead emphasize the cyclical nature and chronicity of cannabis use. Students who do not associate heavy marijuana use with vomiting will miss this diagnosis. The tested pearl here is that capsaicin cream, not ondansetron, is the best acute treatment.

Another trap is the urine drug screen detection window. A vignette may present a patient who last used cannabis three weeks ago and still tests positive. Students may incorrectly conclude this represents recent intoxication. The tested concept is that THC-COOH, being lipophilic, persists in urine for up to 30 days or more with chronic use, and a positive screen alone does not equate to acute intoxication.

Finally, students must differentiate cannabis intoxication from synthetic cannabinoid intoxication. The vignette will often describe a much more severe clinical picture (seizures, severe psychosis, renal failure) and may note that the routine urine drug screen is negative. The key teaching point is that synthetic cannabinoids are full CB1 agonists, are far more dangerous than plant-derived cannabis, and are not reliably detected on standard immunoassay panels.