This is the first installment of an educational reference column on drugs — legal and illegal, common and obscure. It is not a guide to using anything, and it carries no ads: we don’t want a banner selling something next to a table about dependence risk. The goal is the same one a pharmacology textbook or a public-health fact sheet has — lay out what’s actually known, sourced, and let readers draw their own conclusions. We’re starting with one wide comparison table across substance classes. It will grow as we add more columns, more substances, and more depth to each entry.
Two very different ways a drug can respond to dose
Before the table, one piece of pharmacology worth understanding, because it’s a column in it: not every drug behaves the same way as you take more of it. Most familiar drugs are what we’re calling Dial drugs — the effect scales roughly continuously with dose, across a wide, graduated range. More caffeine, more alertness. More alcohol, more impairment. LSD and psilocybin belong here too, even though people don’t always expect that: both have a 30–90 minute onset and unfold over 4 to 12 hours, which leaves real room to feel a genuinely different, titratable intensity across that range — from a barely-there microdose up through a heavy, high-dose experience. It’s a dial with a very long throw, not a light switch.
A smaller group are Switch drugs: onset so fast and duration so short that there’s little room to feel it build — below a threshold dose, not much happens; cross it, and a qualitatively different state turns on within seconds to a couple of minutes, with the whole thing over before a Dial drug would even have fully kicked in. Vaporized DMT and 5-MeO-DMT are the clearest examples: the entire arc is 10 to 30 minutes, and users describe the onset as closer to a light switch than a dial. Smoked salvia is similar. Ibogaine lands in this group for a different reason — not speed (it can run 24 to 36 hours) but the fact that once the threshold is crossed there’s no meaningful way to dial the experience back down, and redosing mid-session is genuinely dangerous. Ayahuasca sits in between — same DMT receptor pharmacology as the vaporized form, but the oral route with an MAOI slows onset to 30–60 minutes and stretches the arc to 4–6 hours, giving it more of the graduated character of a Dial drug without quite the range LSD or psilocybin have; we’re marking it Semi in the table below rather than forcing it into either bucket.
Separately, LSD and psilocybin share something else worth flagging: near-total tolerance after a single dose — a second dose the next day does almost nothing — that resets within about a week, and carries over between the two of them since they hit the same serotonin 5-HT2A receptor. That fast-building, fast-resetting, cross-tolerant pattern with essentially no physical dependence is pharmacologically unusual, and it’s a real part of why these two don’t produce the same compulsive-use patterns that Dial drugs like nicotine or heroin do, even though the tolerance mechanism is unrelated to the Dial/Switch dose-response question above.
The comparison table
Eighteen substances across the classes people actually ask about, side by side. Dose–response is Dial or Switch as explained above. Tolerance describes how fast repeated use blunts the effect. Dependence potential is a qualitative band, not a precise score — it draws on the peer-reviewed multi-criteria harm rankings in Nutt et al. (2010, The Lancet) and DEA/NIDA classification, not on any single number. Legal status is federal U.S. status as of this writing and changes by state and country — treat it as a starting point, not legal advice.
| Substance | Class | U.S. legal status | Dose–response | Typical duration | Tolerance pattern | Dependence potential |
|---|---|---|---|---|---|---|
| Caffeine | Mild stimulant | Legal, unregulated | Dial | 4–6 hrs | Builds over days; resets in about a week off | Low |
| Nicotine | Stimulant | Legal, 21+ | Dial | Minutes (smoked) to hours (patch) | Builds fast; persistent | Very High |
| Alcohol | Depressant | Legal, 21+ | Dial | 1–3 hrs per standard drink | Builds with chronic use; physical dependence | High |
| Cannabis (THC) | Cannabinoid | Legal in some states; Schedule I federally | Dial | 2–4 hrs smoked/vaped; 4–8 hrs edible | Moderate; receptor downregulation with daily use | Low–Moderate |
| Cocaine | Stimulant | Schedule II | Dial | 20–30 min insufflated | Moderate; binge/crash pattern | High |
| Methamphetamine | Stimulant | Schedule II | Dial | 8–12 hrs | Builds fast | High |
| MDMA | Empathogen | Schedule I (in FDA trials) | Dial, with a ceiling | 3–5 hrs | Builds very fast; sharp serotonergic rebound | Low–Moderate |
| Heroin / opioids | Opioid | Schedule I (heroin); Rx opioids Schedule II | Dial | 4–5 hrs | Builds fast; strong physical dependence | Very High |
| Benzodiazepines | Depressant | Schedule IV (prescription) | Dial | 4–12 hrs, agent-dependent | Builds with daily use; dangerous physical withdrawal | High |
| Ketamine | Dissociative | Schedule III (esketamine Rx-approved) | Dial toward a dissociative ceiling | 45–90 min | Moderate; urinary-tract harm with heavy chronic use | Moderate |
| LSD | Classic psychedelic | Schedule I | Dial, wide range | 8–12 hrs | Near-total after one dose; resets in ~1 week; cross-tolerant with psilocybin | Very Low |
| Psilocybin (mushrooms) | Classic psychedelic | Schedule I (some local decriminalization) | Dial, wide range | 4–6 hrs | Near-total after one dose; resets in ~1 week; cross-tolerant with LSD | Very Low |
| Ayahuasca (DMT + MAOI) | Classic psychedelic, oral | Schedule I ingredient; religious-use exemptions exist | Semi — slower-onset DMT | 4–6 hrs | Resets quickly | Very Low |
| DMT (vaporized) | Classic psychedelic | Schedule I | Switch, very sharp | 10–20 min | Resets quickly | Very Low |
| 5-MeO-DMT | Classic psychedelic | Schedule I | Switch, very sharp | 15–30 min | Resets quickly | Very Low — high physiological intensity, distinct risk profile |
| Ibogaine | Atypical psychedelic | Schedule I | Switch, very long-acting | Up to 24–36 hrs | Rarely redosed (see risk note) | Very Low — cardiac arrhythmia risk; deaths reported |
| Salvia divinorum | Dissociative psychedelic (kappa-opioid) | Legal federally; banned in some states | Switch, extremely sharp | 5–15 min smoked | Rapid | Very Low |
| Datura | Deliriant (anticholinergic) | Legal to possess as a plant; sale sometimes restricted | Switch, but unpredictable | 24–48+ hrs, unpredictable | Some | Low addictive potential — very high physical danger; common cause of accidental poisoning and death; not comparable in risk to the psychedelics above |
Low addiction risk is not the same as low risk
The table’s biggest trap, if you only skim the “dependence potential” column, is concluding that a Very Low badge means a substance is safe. It doesn’t. Datura is barely habit-forming — almost no one takes it repeatedly, largely because the experience is unpleasant and the dosing is genuinely unpredictable from plant to plant — and it is also a leading cause of accidental poisoning deaths among the substances in this table, with a fatal dose sitting uncomfortably close to a recreational one. Ibogaine has one of the lowest dependence profiles here and a well-documented risk of fatal cardiac arrhythmia, which is exactly why it’s administered under medical monitoring in the clinics that offer it legally outside the U.S. 5-MeO-DMT is the most physiologically intense compound in this list by most subjective-effects research, disproportionate to its brief duration. Addiction potential, physical danger, and overdose risk are three different axes, and a responsible comparison keeps them separate rather than collapsing them into one score.
This column will keep expanding: overdose-risk and drug-interaction columns, route-of-administration detail, and profiles on individual substances are next. If you or someone you know is struggling with substance use, the SAMHSA National Helpline (1-800-662-4357) is free, confidential, and available 24/7.
