Cocaine

Aliases: Coke, Blow, Snow, Crack (freebase form)

Chemical Class: Tropane alkaloid | Risk: high | Schedule: II

Mechanism: Blocks reuptake of dopamine, norepinephrine, and serotonin (triple reuptake inhibitor). Also acts as a sodium channel blocker (local anesthetic effect). Crack cocaine is the freebase form, which vaporizes at lower temperatures allowing inhalation.

Onset/Duration by Route

Desired Effects: Intense euphoria, Increased energy and alertness, Confidence and sociability, Decreased appetite, Mental clarity (perceived), Local anesthesia

Adverse Effects: Tachycardia, hypertension, Vasoconstriction, Hyperthermia, Bruxism (jaw clenching), Anxiety, paranoia, agitation, Insomnia, Nasal septum perforation (insufflation), Respiratory damage (smoking), Seizures at high doses

Overdose: Lethal dose varies widely (individual tolerance, ROA, purity). Deaths typically from cardiac arrhythmia, MI, stroke, or hyperthermia. No specific antidote; treatment is supportive (benzodiazepines for agitation, cooling for hyperthermia). Avoid beta-blockers (unopposed alpha stimulation).

Dangerous Interactions

• Alcohol (dangerous): Forms cocaethylene in the liver, which is more cardiotoxic than either substance alone and has a longer half-life
• MAOIs (deadly): Hypertensive crisis risk due to massive catecholamine surge
• Other stimulants (dangerous): Additive cardiovascular strain; risk of heart attack, stroke
• Opioids (speedball) (deadly): Opposing effects mask overdose signs; cardiac arrhythmia risk

WARNING: Fentanyl contamination risk. Always test your supply with fentanyl test strips.

Amphetamine

Aliases: Speed, Adderall, Dexedrine, Vyvanse (prodrug)

Chemical Class: Substituted phenethylamine | Risk: high | Schedule: II

Mechanism: Releases dopamine, norepinephrine, and serotonin from presynaptic vesicles via TAAR1 agonism and VMAT2 inhibition. Also inhibits reuptake transporters (DAT, NET). Dextroamphetamine (d-amp) is more potent at dopaminergic effects; levoamphetamine (l-amp) is more noradrenergic.

Onset/Duration by Route

Desired Effects: Euphoria (especially at recreational doses), Enhanced focus and concentration, Increased motivation and productivity, Wakefulness, Decreased appetite, Increased sociability and confidence

Adverse Effects: Tachycardia, hypertension, Dry mouth, Insomnia, Appetite suppression (significant weight loss), Anxiety, irritability, Bruxism, Erectile dysfunction, Psychosis at high doses or with chronic use

Overdose: Symptoms: severe hypertension, hyperthermia, seizures, rhabdomyolysis, serotonin syndrome (with serotonergic drugs). LD50 poorly defined in humans (5-30 mg/kg estimated). Treatment: benzodiazepines for agitation/seizures, cooling, IV fluids.

Dangerous Interactions

• MAOIs (deadly): Hypertensive crisis due to massive norepinephrine/dopamine release
• SSRIs (caution): Possible serotonin syndrome at high doses; generally safe at therapeutic levels
• Other stimulants (dangerous): Additive cardiovascular strain
• Acidifying agents (vitamin C) (caution): Increases renal excretion, reduces effectiveness

WARNING: Fentanyl contamination risk. Always test your supply with fentanyl test strips.

Methamphetamine

Aliases: Meth, Crystal, Ice, Tina, Glass, Crank

Chemical Class: Substituted phenethylamine (N-methylamphetamine) | Risk: extreme | Schedule: II

Mechanism: Same mechanism as amphetamine but with higher lipophilicity allowing faster CNS penetration. More potent dopamine release than amphetamine. Also causes significant serotonin release (contributing to neurotoxicity). TAAR1 agonist, VMAT2 inhibitor, and monoamine reuptake inhibitor.

Onset/Duration by Route

Desired Effects: Intense, prolonged euphoria, Extreme energy and wakefulness, Hyperfocus, Increased libido, Confidence and sociability, Weight loss

Adverse Effects: Severe tachycardia, hypertension, Hyperthermia, Bruxism (meth mouth contributing factor), Insomnia (days without sleep possible), Paranoia, hallucinations, psychosis, Skin picking (formication), Compulsive/repetitive behavior, Aggression

Overdose: Symptoms: hyperthermia (primary cause of death), seizures, cardiac arrhythmia, intracranial hemorrhage, rhabdomyolysis. No antidote. Treatment: aggressive cooling, benzodiazepines, supportive care.

Dangerous Interactions

• MAOIs (deadly): Hypertensive crisis
• Serotonergic drugs (dangerous): Serotonin syndrome risk (meth releases serotonin)
• Other stimulants (dangerous): Extreme cardiovascular strain
• Opioids (deadly): Goofball/speedball: masks overdose signs from either drug

WARNING: Fentanyl contamination risk. Always test your supply with fentanyl test strips.

MDMA

Aliases: Ecstasy, Molly, XTC, E, Mandy

Chemical Class: Substituted amphetamine (3,4-methylenedioxymethamphetamine) | Risk: moderate | Schedule: I

Mechanism: Primarily a serotonin releaser via SERT reversal. Also releases dopamine (via DAT) and norepinephrine (via NET). Inhibits monoamine reuptake. The massive serotonin release (80% of effect) produces the characteristic empathogenic/entactogenic experience. Also releases oxytocin and vasopressin.

Onset/Duration by Route

Desired Effects: Euphoria and emotional warmth, Empathy and emotional openness, Enhanced sensory perception, Increased sociability and prosocial behavior, Reduced anxiety and fear, Enhanced music appreciation, Feelings of love and connection

Adverse Effects: Bruxism and jaw tension, Nausea (come-up), Hyperthermia (potentially fatal in hot environments), Hyponatremia (from excessive water intake), Tachycardia, hypertension, Dilated pupils, Appetite suppression, Post-use depression ("suicide Tuesday"), Insomnia

Overdose: Primary risks: hyperthermia (>41C/106F), hyponatremia (dilutional from excessive water + ADH secretion), serotonin syndrome, DIC, multi-organ failure. Deaths often involve combination with other drugs or overheating in hot environments. Treatment: cooling, isotonic saline, benzodiazepines, cyproheptadine (for serotonin syndrome).

Dangerous Interactions

• MAOIs (deadly): FATAL serotonin syndrome. Includes ayahuasca, moclobemide, phenelzine, and some research chemicals
• SSRIs/SNRIs (dangerous): Serotonin syndrome risk. SSRIs also block MDMA effects. Do not combine
• Tramadol (deadly): Serotonin syndrome and seizure threshold lowering
• DXM (dangerous): Serotonin syndrome risk due to DXM's SRI activity
• Lithium (dangerous): Potentiates serotonin effects, seizure risk

WARNING: Fentanyl contamination risk. Always test your supply with fentanyl test strips.

Caffeine

Aliases: Coffee, Tea, Energy drinks, Caffeine pills

Chemical Class: Methylxanthine (1,3,7-trimethylxanthine) | Risk: low | Schedule: None

Mechanism: Adenosine receptor antagonist (primarily A1 and A2A). Blocks the sleep-promoting effects of adenosine, leading to increased wakefulness. Also inhibits phosphodiesterase (increasing cAMP), releases intracellular calcium, and promotes dopamine signaling indirectly via adenosine-dopamine receptor interactions.

Onset/Duration by Route

Desired Effects: Increased alertness and wakefulness, Enhanced concentration and focus, Reduced fatigue, Improved physical performance (2-5%), Elevated mood, Bronchodilation

Adverse Effects: Anxiety and jitteriness, Insomnia, Tachycardia, palpitations, GI upset, acid reflux, Frequent urination (mild diuretic), Headache (withdrawal), Tremor at high doses

Overdose: LD50: approximately 150-200 mg/kg (10-14g for a 70kg adult). Caffeine powder overdoses have caused deaths. Symptoms: seizures, cardiac arrhythmia, rhabdomyolysis. Pure caffeine powder should be treated as a drug, not a supplement.

Dangerous Interactions

• Ephedrine/pseudoephedrine (caution): Additive cardiovascular stimulation
• Lithium (caution): Caffeine increases lithium clearance; abrupt cessation can raise lithium levels
• Adenosine (medical) (caution): Caffeine blocks adenosine effects; higher doses of adenosine may be needed

Nicotine

Aliases: Cigarettes, Vaping, Chewing tobacco, Snus, Patches, Gum

Chemical Class: Pyridine alkaloid (nicotinic acetylcholine receptor agonist) | Risk: high | Schedule: None (but tobacco heavily regulated)

Mechanism: Agonist at nicotinic acetylcholine receptors (nAChRs), primarily alpha-4-beta-2 subtype in the CNS. Stimulates dopamine release in the nucleus accumbens via VTA activation. Also releases norepinephrine, acetylcholine, serotonin, and glutamate. Combustion products (tar, CO, etc.) cause most health damage, not nicotine itself.

Onset/Duration by Route

Desired Effects: Relaxation and stress relief (withdrawal relief), Increased alertness, Improved concentration, Appetite suppression, Mild euphoria (mainly in non-tolerant users), Anxiolytic effects

Adverse Effects: Nausea and dizziness (especially initial use), Increased heart rate and blood pressure, Vasoconstriction, Insomnia, GI disturbances, Nicotine poisoning in children/pets (liquid nicotine, pods)

Overdose: LD50: 40-60 mg for adults (older estimate; may be higher). Children and pets at high risk from liquid nicotine/e-liquid. Symptoms: nausea, vomiting, seizures, cardiac arrhythmia. Treatment: supportive, atropine for bradycardia.

Dangerous Interactions

• Medications (many) (caution): Smoking (not nicotine per se) induces CYP1A2, affecting metabolism of caffeine, theophylline, clozapine, olanzapine, and many others. Dose adjustments needed when starting/stopping smoking.
• Hormonal contraceptives (dangerous): Smoking + estrogen-containing contraceptives greatly increases thromboembolism risk, especially in women >35