The market for legal—or until recently legal—highs is booming. A recent report by the EU’s drug agency, for example, shows that it is currently monitoring a staggering 280 of them. What exactly are these myriad substances? Thanks in part to the media’s habit of lumping them together into one scary whole—with regular outbreaks of frenzy, such as with Bath Salts last year—they often remain shrouded in mystery and rumor.

To get closer to the truth I decided to ask Jeff Lapoint, MD, an attending physician in emergency medicine and medical toxicology at Kaiser Permanente in San Diego, who is also a former senior toxicology fellow at New York University’s Bellevue Hospital. He’s an expert who both understands these drugs’ complex chemistry and, through his work with New York City’s Poison Control, has hands-on experience of how these drugs can affect users. Despite having seen the dark side of these substances, he retains a cool head when it comes to the future of this market, recognizing that harsher laws will do nothing to help users, and that there’s no such thing as a “bad” chemical. But in their current unregulated condition—with dosing, toxicity, cuts, etc., all a crap shoot—using some of these chemicals as drugs can be very bad indeed.

Legal highs vary wildly in their effects—and have-a-go chemists are constantly developing new compounds. Trying to map such a market isn’t easy, but with Lapoint’s expertise—and some user experiences, including one or two of my own—we’ll make a start.

1. Synthetic Cannabinoids (Spice, K-2, etc.)

“Man has been smoking marijuana for 4,000 years,” says Dr. Lapoint. “That’s a pretty damn good human trial. Compare that to five years of synthetic cannabinoids. We have no idea what the long-term effects of those might be, and that’s scary.” Lapoint concedes that the debate on the medical properties of marijuana is still up for grabs, though “what you cannot argue with is marijuana’s safety.” But he warns that synthetic cannabinoids are an entirely different ball game. In fact, he says, calling this stuff “synthetic marijuana” at all is a fallacy.

Synthetic marijuana briefly took off among users who enjoyed the novelty of a legal drug that actually worked. Experiences ranged from the sublime: “I felt a very familiar sensation of ‘getting high’ exactly as if I had just hit some decent bud,” to the terrifying: “Marijuana is simply lovely. However, I consider Spice to be the lovely Mary Jane's psychotic sister that stays locked in the attic, chained to a pole and wearing a muzzle.”Synthetic cannabinoids have been sold under countless brand names; the more famous include Spice, K2 and Black Magic. As with many legal highs, the ingredients listed on the package usually comprise a selection of allegedly benign legal herbs, but lab testing tells a different story. The psychoactive effects are caused by spraying certain chemicals—most commonly JWH-018,HU-210 and CP-47/497—onto the plant material. Their active ingredients are lab-tweaked variations of THC—pot’s active ingredient—that often “do not even [structurally] look like THC anymore,” says Lapoint. “The only similarity between this stuff and marijuana is that these substances bind to cannabinoid receptors in the brain. This is worrying because we do not fully understand these receptors.” Some synthetic cannabinoids bind to these receptors up to 100 times more effectively than THC, with wildly unpredictable effects, including psychosis and depression.

Last year the US government outlawed many of the more popular synthetic cannaboids, but there is almost no end to the tweaking that can be done to THC’s chemical structure. Chances are, the next wave of “synthetic marijuana” will act even less like pot than the first. Lapoint compares the dangerous boom in these substances to the mass production of dangerous bathtub hooch during Prohibition. “The sad truth is that there is a safer substance that humankind has extensive experience with, yet it remains illegal.”

2. 2M2B

2M2B (2-methyl-2-butanol) is used primarily as a pharmaceutical or pigment solvent but has recently been popping up for sale—usually in doses of five or 10 ml—on legal high sites. It is marketed as a depressant and intoxicant, and the chatter on drug forums suggests that it’s beginning to catch on. “We don’t see it out there a lot, and my comments are purely theoretical,” Dr. Lapoint says, adding that on a purely chemical level 2M2B is a fascinating substance.

Despite these dangers, small groups of 2m2b users are posting enthusiastic reports, its nasty camphor-like taste notwithstanding. They describe an initial rush—“[7.5 ml] feels like 5 shots of vodka. Slightly wobbly, focusing becoming harder” that leads to “somewhere between benzos and ethanol.” While it remains to be seen if this compound will find mass appeal, there are at least five vendors in the UK alone. (In the world of legal highs, Britain and Europe often act as testing grounds for substances that later find popularity in the US.)It acts upon the same GABAa receptor as ethanol—the active ingredient in booze—but has some unique characteristics. “It’s not metabolized the same way that ethanol is,” Lapoint explains. “Ethanol has to be broken down by two specific enzymes in your body. We can actually block those, with Antabuse, for example. By playing with those enzymes you can even make people get an instant hangover when they drink booze.” But 2M2B is broken down differently and has one startling advantage over traditional cocktails: no hangovers. “Imagine if you could get drunk and not pay the piper,” Lapoint says. “That’s what makes it so attractive as a substance of abuse. However, it’s maybe several thousand times more potent than ethanol on the sedative/hypnotic scale, which brings up some serious risks like respiratory depression.” This makes it less booze than barbiturate.

3. Bromo Dragonfly

This extremely potent psychedelic has a small but devoted following of psychonauts. Dave Nichols’ team at Purdue Pharmaceuticals originally designed the chemical behind Bromo Dragonfly to further research the brain’s serotonin receptors, which are the targets of hallucinogenic and some prescription anti-psychotic drugs. Nichols has since expressed his regret that his work inadvertently gave rise to this dangerous legal high. Dr. Lapoint—hardly prone to “drugs are bad, m’kay” hysteria—simply describes this substance, which is sold in powder or blotter form, as “terrifying.”

Bromo Dragonfly made headlines in 2009 when it was linked to at least two deaths and several hospitalizations, after being mislabeled and sold as a different designer drug by a Chinese vendor. Even those who ingest it knowingly are liable to hit problems. “This substance just tends to produce a very gross toxic chemy feeling,” one user reports. “And I could definitely see OD'ing on Bromo Dragonfly being one of the shittiest ways to leave this world. So be safe, fellow travelers.”Users all seem to agree that Bromo Dragonfly takes a long time to kick in—up to five hours. “I dosed the same time [as my friend] took acid, and by the time I was only just starting to peak, [he] was already down from the peak into the plateau,” one user says. Others also report extremely potent psychedelic effects: “I heard drums turning into children’s voices and ocean waves. The real world turned into a mosaic-like grid. Trees were bursting apart into fractals. Walls turned invisible.”

Another potential danger is severe narrowing of the blood vessels and constriction of blood flow. Lapoint mentions an infamous case in Sweden in which a user’s “extremities just died.” He survived, but lost all the fingers on his left hand and several toes. Couple the slow onset with the high potency, and the truth is that it’s incredibly easy to accidentally overdose on this drug. Lapoint warns that “Bromo Dragonfly is probably the scariest thing on this list.”

4: O-Desmethyltramadol

Given the backlash against doctors over-prescribing painkillers, a legal compound mimicking the effects of opioids might be widely seen as a Holy Grail. O-Desmethyltramadol is the active metabolite of tramadol—a prescription analgesic painkiller that is weaker and typically less prone to abuse than the likes of oxycodone. Recreational users are beginning to share their experiences via specialist websites. Some are enthusiastic, while one writes, “It definitely feels like an opioid, but it is very much lacking in that classic opioid euphoria that we all use for.”

I can relate. As a one-time aficionado of opiates, when I was prescribed tramadol I found it a deeply unpleasant experience.Sold as a powder that can be snorted or swallowed, many users report the effects of O-Desmethyltramadol as being on a par with buprenorphine or tramadol. And there, says Lapoint, lies the rub: “Some people love the novel psychoactive effects of tramadol. Theoretically, while Tramadol is an opioid agonist that hits the same receptors as other narcotic painkillers, it also works on the serotonin neurotransmitter—the target of many anti-depressants. Many people find it causesdysphoria—feelings of emotional or mental discomfort.

A tramadol-derived drug also raises an interesting “what if” about unregulated legal derivatives of narcotic painkillers. So far Lapoint hasn’t seen it widely used. “Of course,” he says, “even if they wind up in the ER, finding if someone has used this particular substance versus other opiates will be a game of CSI.”

5. 2C-P

2C-P is a synthetic psychedelic and a close chemical cousin of 2C-B, which briefly thrived on the US club scene until it was outlawed in 2001. Users report that 2C-P—which itself was made illegal in the US last year—causes stronger visual hallucinations and way longer effects: “at least 16 hours of very good visually and mentally tripping,” writes one. As with all psychedelics, the quality of the trip depends a lot on the psychological state of the user. While some praise 2C-P’s “interesting, powerful and enlightening” effects, others find the experience “somewhat disturbing. I wish I had never thought of some of the things I thought of during that long, sleepless night.”

“If you look at Alexander Shulgin’s book PIHKAL[Phenethylamines I Have Known and Loved], he gives you a cookbook and a user report on every one of these compounds,” Dr. Lapoint says. “While Shulgin really loved the effect of 2C-P, ever since this compound found its way to the gray market, there have been horrible cases—a recent incident in Minnesota, for example, where people may have actually gotten Bromo Dragonfly.” One teen died and ten others were hospitalized.2C-P is a phenethylamine, a class of chemicals that release high amounts of dopamine and/or serotonin. 2C-P is classified as an amphetamine because it mainly targets dopamine—the brain chemical responsible for stimulant reactions. But it also targets serotonin—the brain chemical behind hallucinogenic effects. In fact, 2C-P’s hallucinogenic effects are more powerful than its stimulant ones.

As with most of these drugs, you rarely know what you’re really ingesting. “If you are Alexander Shulgin and make it yourself, that’s one thing,” says Lapoint. “As far as buying it from some anonymous vendor? That’s always sketchy.”

6. Mephedrone (Bath Salts)

Similar in structure to methamphetamine but tweaked slightly to bypass the law and produce a more hallucinogenic effect, mephedrone—actually a derivative of the Somali drug khat—first found cult popularity in clubs around the world as a cheap, legal upper. It attracted little attention when it first spread to the US. Then in 2012 a Florida man called Rudy Eugene committed one of the most infamous acts of cannibalism since the Donner Party, and a new media menace was born: Bath Salts. By the time Eugene’s autopsy found only marijuana in his system it was too late: Bath Salts had been irreversibly linked to outlandish insanity and violence.

Why is this so with mephedrone, while ecstasy—which also has both stimulant and hallucinogenic properties—is not linked with extreme behavior? Ecstasy—whose active ingredient is MDMA—is an enigmatic and unique substance, Lapoint says. “While MDMA is a substituted amphetamine, it is what we call an empathogen. You don’t hallucinate when you take E. Instead you experience a feeling of being a part of something and a desire to share. However, mephedrone works in a very different way, despite the surface chemical similarities.That’s not to say that mephedron is benign. “These are stimulants that tend to have hallucinogenic properties,” Dr. Lapoint says. “That’s a bad combo.”

“It may not be the worst thing to be a little amped up,” Lapoint concedes. “But when someone who is amped up and hallucinating, it’s a crap shoot. How will they react? Will they get paranoid or violent? There’s an infamous story about a guy in Florida who was arrested in drag after eating his neighbor's goat!”

7. 6-APB (Benzo Fury)

Benzo Fury hit the UK club scene in 2010. Users often call it “a mixture of ecstasy and cocaine,” or simply similar to good-quality E: “feeling blissed out of my mind. With each crisp ocean breeze comes another wave of immense joy and sensual decadence.” 6-APB is structurally similar to MDA—and therefore more powerful than X. However, it’s considerably less powerful in its empathic effects. Negative experiences reported tend to emphasize its “speedy” and jittery side. Since Benzo Fury became popular—partly thanks to tabloid hysteria that helped alert many to its existence—unscrupulous sellers have been packaging a wide variety of research chemicals as “Benzo Fury.” (Again, it's worth noting that this unregulated, “Wild West” aspect of the legal highs market may be its biggest risk.)

Interestingly, in Britain and Australia, its huge popularityseems to be a direct reaction to the “success” of anti-drug initiatives that made good-quality MDMA scarce. The UK has now moved to ban Benzo Fury for 12 months while it is “assessed.” (If the country’s experience with mephedrone is anything to go by, the trade will soon move from the Internet to street corners, where users report that prices have doubled while purity levels have crashed.) “This is a substituted amphetamine, in the same area as Bath Salts or designer amphetamines,” says Dr. Lapoint. “We’re not seeing a lot of it in the US market yet, but so far the big problems associated with this substance seem to be hyperthermia and seizures.”

8. Salvia

A few years before the Great Bath Salts Scare, there was the Salvia Terror of 2010, with young users posting YouTube videos of themselves tripping after smoking this herb (which is actually related to mint). When the media rang the alarm, its use skyrocketed. The frenzy hit its peak later that year when a video of pop princess Miley Cyrus allegedly smoking salvia hit TMZ. The fact that Hannah Montana was now using the stuff caused enough of a political freak-out that some states rushed to have Salvia banned as a Schedule I drug, like heroin or cocaine. But as the media’s attention waned so did the politicians’, and this psychedelic herb—smoked by shamans throughout history—has sunk back into semi-obscurity. It remains legal in most of the US.

Smoking salvia causes a short, intense trip that is primarily dissociative in nature. I smoked it once and found it interesting, but not an experience I was eager to repeat. Unlike drugs that flood the brain with serotonin, or classic psychedelics that fully derange the senses, salvia is a pretty shallow experience—one step up from poppers or whippets. The real danger, as with most perception-altering substances, is the immediate impairment. Disorientation and confusion are common, and it was salvia’s unintended comedic aspects that fueled the Youtube craze.Salvia is classified as a hallucinogen. However, its mechanism of action in the brain is entirely different from synthetic hallucinogens like LSD. It is extremely potent, but it is not toxic. In lab tests animals have been exposed to huge doses without harm.

Dr. Lapoint says that salvia isn’t the demon drug it was once portrayed as, although, “We don’t see a lot of salvia cases in Poison Control. Maybe it’s an issue of misdiagnosis—if someone comes into the ER hallucinating, often the doctors will just assume they’re on PCP. If you get sick and it’s a stimulant, they will assume it’s coke. New York is classically a heroin or cocaine town and I think we miss a lot of these new drugs because of that old-school mentality.” Still, Lapoint says that salvia’s short-acting nature makes it way less dangerous than some of the other substances on this list.

9. Methoxetamine (Mexxy)

A chemical analogue of ketamine and PCP, it is, like them, classified as a dissociative anesthetic type of hallucinogen. Methoxetamine has been sold since 2010 and found massive popularity on the European club scene. Mixmag says the drug is sometimes called “rolfcoptor,” as well as its street name “Mexxy.” Sold as pellets or a powder that is usually snorted (though sometimes IV’d), user reports tend to emphasize that this is not a drug to be taken lightly: “Overall the trip was enjoyable, there were a few parts which could easily have been scary such as thinking I was going to die but they passed rather quickly.” A number of people have reported that the drug creates an urge to compulsively take more, leading to some terrifying overdoses: “I began having severe stomach upsets, with alternating diarrhea and vomiting. The diarrhea looked strange and red, as if there was blood in it, as did the vomiting. I was overcome with the idea that this night would be my last.”

Dr. Lapoint notes that methoxetamine use is still in its infancy in the US. But the story of how methoxetamine came to be a drug of abuse is indicative of the futility of lawmakers’ current approach. “It’s a shell game between those who create these substances and those who seek to ban them,” he says. “Tweak the formula and you have a brand-new substance with users completely unaware of how they will react to it and what the long-term effects are.” In the case of methoxetamine, the process of chemical substitution has created a legal high that some have compared to high-dose DXM (the active ingredient in many over-the-counter cough medicines).

10. Kratom

The kratom plant (Mitragyna speciosa) has long been used as a stimulant and painkiller and remains legal in many countries, including the US. First favored by laborers in Thailand, who have chewed its leaves for centuries, it has recently become more widely available via the Internet. It is most often sold as a powder. Users make tea from it, or it is “tossed and washed”—a teaspoonful of the (reportedly) foul-tasting substance is placed on the tongue and washed back with water. Fans describe kratom as a benign herb that mimics the effects of low-dose opiates without the risk of addiction. Some posters in the thriving online community of kratom advocates describe kicking debilitating painkiller habits by using kratom as a tapering agent.

Kratom has the “most hopeful” prospects for medical use, Dr. Lapoint says. It mostly hits the kappa-opiod receptors, like traditional opiates. But unlike them, kratom doesn’t cause respiratory depression. So in theory a painkilling drug could be derived from kratom that has all of the positive effects of, say, codeine, but no risk of overdose. “I think kratom has tremendous potential as a tool to treat the epidemic of opiate addiction in the US,” says Lapoint.When taken orally, kratom causes a mild euphoria effect, along with a mild stimulant effect often likened to a cup of espresso. But kratom’s mildness hasn’t stopped it from being lumped in with more dangerous drugs.

Yet despite this promise, drug companies are hardly rushing to investigate. In fact the typical response so far has been some half-hearted attempts at whipping up a media scare and a handful of opportunistic politicians threatening to ban it. (The Seattle-based alternative weekly, The Stranger, has a clear-eyed report on the rush to outlaw this potentially helpful herb.) “The fact that this is a leaf traditionally chewed by indigenous people makes it harder for the medical establishment to swallow,” says Lapoint.