Clearing the air on 'synthetic cannabis': a primer

There has been a public backlash against the use of the term "synthetic cannabis", on the basis that these drugs have nothing to do with natural cannabis. On one level, this is evidently true. There are seven major groups of synthetic cannabinoids. While some, including HU-210 (banned in New Zealand in 2014), are structurally similar to THC, the main psychoactive cannabinoid in natural cannabis, most are not.

The reason that most researchers continue to characterise this disparate group of chemicals as synthetic cannabinoids is that they are agonists for – that is, they act on – the same CB-1 and CB-2 receptors in the brain and central nervous system as THC does. Some commentators prefer the term cannabimimetics – meaning chemicals that act like cannabinoids.

Not all cannabimimetics are bad. Nabilone (a synthetic analogue of THC) and dronabinol are both used to treat nausea in cancer patients and even paracetamol metabolises into a chemical that acts on the receptors. Typically, those in illicit use are full agonists for the receptors, which means their effect is vastly stronger than that of THC, which is only a partial agonist.

Their effects are poorly understood – they may act on other receptors, or interact badly with other drugs or even with each other (it's common for smoking mixtures to contain more than one cannabinoid).

Nearly all of them also have structures that allow them to volatise readily when smoked, which made them suitable candidates to enter the market in the way they did: as smokeable cannabis substitutes. Typically, the chemical is dissolved in a solvent (usually acetone) for spraying on vegetable matter – damiana herb, marshmallow leaves or even natural cannabis.

In many other countries, the brand names of early commercial products have become generic terms for synthetic cannabis products. So British newspapers use "Spice" as a catch-all and the Americans refer to "K2". In Nigeria, "Black Mamba" caught on. In New Zealand, these brand names have also become generic, but the most common street name is "synnies".

In New Zealand, since about 2006, when a product under the Spice brand appeared in stores. That contained a synthetic cannabinoid called CP 47,497, which was so similar to THC that it fell afoul of the analogue provisions of the Misuse of Drugs Act. The Expert Advisory Committee on Drugs found in 2010 that other chemicals, such as JWH-018 and JWH-073, entered the market only after the first one was banned. They in turn were banned, so new and possibly more harmful cannabinoids replaced them.

Some of these were briefly regulated for sale under the interim approval provision of the Psychoactive Substances Act, before an amendment to the act ushered in a blanket ban. The substitution effect did not stop there, however. China's banning of several cannabinoids pushed manufacturers there to move on to new chemicals.

No. The suggestions floating around, including from the NZ Police, that additives including flyspray and weed killer are added doesn't stack up. While it's likely that some consumers – who are no position to verify the contents of their drugs – have purchased such homemade concoctions, the evidence strongly suggests that's not the problem. Likewise, while we've been told of one batch being sprayed with the ketamine analogue methoxetamine (MXE), that does not seem to be at all common. 

The symptoms described by emergency medics are consistent with known reactions to synthetic cannabinoids. And it's not only New Zealand seeing such alarming casualties at present. In recent weeks, a spate of 20 overdoses in 24 hours was attributed to a “bad batch” of Spice in Fort Wayne, Indiana, and one county in Pennsylvania struggled to cope with 158 ODs in seven days. The local emergency services director told reporters that "some bad K2 has hit the street". 

The chief suspect for the wave of deaths and acute reactions in New Zealand is the synthetic cannabinoid AMB-FUBINACA (aka FUB-AMB) which was first synthesised by Pfizer as a potential new painkiller and hit the street in 2014. Although it's structurally related to AB-FUBINACA, which appeared in some products briefly granted interim approval under the Psychoactive Substances Act, AMB-FUBINACA appeared in New Zealand only after all new psychoactive substances were pre-emptively banned when the act was amended. 

One user in a Reddit forum characterised AMB-FUBINACA as "Very potent, but very short acting. It's the crack of synth noids." 

That potency has dosing implications. In "psychonaut" forums, users describe the kind of doses usually associated with LSD – as little as 100 micrograms. ("Respect this chemical, one slip up can put you in the ground," wrote another Reddit contributor.) Sophisticated users often vapourise their "noids".

This kind of dosing precision is difficult to achieve without very precise scales – and almost impossible to do consistently with a solution sprayed on leaves. It seems highly likely that the issue in a "bad batch" is not impurities, but dose. 

Let's say that again: dose.

At very low doses, most synthetic cannabinoids have an effect that somewhat resembles a strong cannabis high. At higher doses, they act as dissociatives – that is, they block out the world, or make it seem unreal. Users may behave bizarrely as a consequence. It's no accident that their use everywhere has spread among people, such as the homeless, who have cause to try and forget their circumstances.

Some very bad things can happen to users. Case studies report respiratory depression, cardiac arrest, seizures, rapid loss of blood pressure leading to unconsciousness and organ damage. Even a non-fatal overdose can result in permanent damage to the liver or kidney.

Wellington Hospital emergency medicine special Dr Paul Quigley says presentations in New Zealand fall into three main categories:

• Increased anxiety (paranoia) with associated insomnia
• Palpitations and cardiac arrhythmia (irregular heartbeat), with the most common being atrial fibrillation (a sustained racing heartbeat, normally a rare event in young people).
• Seizures

Because synthetic cannabinoids are typically quite short-acting, the large majority of patients "come right" within half an hour and need only treatment with a relaxant such as lorazepam to address anxiety. Seizures are also usually of short duration.

Risk factors include underlying cardiac abnormalities, which may be "unmasked" by drug use. The use of other drugs – especially solvents, which are cardiotoxic in their own right – increases the risk of fatal arrhythmias and other dangerous conditions.

The most serious cases are those who have aspirated (breathed in) their vomit while having a fit. They can need treatment in ICU and be very ill indeed.

Dr Quigley notes that ED presentations are actually very rare countrywide. Some centres have seen none at all since synthetic cannabis products were removed from retail sale two years ago. Auckland's experience is not the national experience.

Dependence is a significant issue, perhaps because of the relatively short duration of the drugs' effects. But both Higher Ground and CADS have told us that they're not seeing a flood of presentations, even in Auckland – and the number of clients coming to Auckland Community Alcohol and Drug Services (CADS) was higher during the years when synthetic cannabis products were told nationally in shops.

 According to a paper for the Australasian Professional Society on Alcohol and other Drugs, 47 clients with synthetic cannabis dependence were admitted to CADS' Medical Detoxification Service (MDS) in Auckland between May 2013 and 2014, the period covering regulated sale under the PSA. (This does not mean those problems arose as a result of the Act – dependent users typically take years before they seek help.) The paper noted that synthetic cannabinoids generated six times as many admissions as natural cannabis.

 But even at peak, synthetic cannabis admissions were 4% of the total. By comparison, 74% involved alcohol. Among illicit drugs, both services say their major source of admissions, by far, is methamphetamine.

 It may be significant that while the 2013-2014 paper found that "coexisting substance dependence apart from nicotine dependence was low," most CADS clients presenting with synthetic cannabis problems in 2017 do have coexisting dependence issues with a range of other drugs.

 We currently know virtually nothing of the long-term effects of these drugs.

China. 

The Chinese drug factories that churned out synthetic cannabinoids for retail sale in New Zealand did not close down when they were banned here. And you won't need to go on the "dark web" to find them.

Matters of Substance was able to easily locate manufacturers in China. XioSun Research Chemicals, for example, was offering AMB-FUBINACA in quantities from 10g ($US125) to 1kg ($US1900). And that's not all: the same company listed the depressant etizolam as its top seller, along with MXE and the MDMA substitute 6-APDB. When we checked, alpha-PVP crystals were on special, down from $2900/kg to $1800.

To look at these sites is to be reminded that the synthetic cannabinoids are just one part of a group of new psychoactive substances (NPS) that now runs into the thousands, from depressants to psychedelics. New chemicals, with new properties, can be created simply by tinkering with molecules. Nearly all of them are poorly understood.

Essentially, anything not specifically controlled internationally by the UN drug conventions – and no synthetic cannabinoids are – will be produced by these factories. They're not always making psychoactives – most will also produce standard pharmaceuticals to order – but it's not hard to see that they're not quite in the daylight either. Bitcoin tends to be the preferred medium of exchange, and some producers offer reshipment from a third country as an additional service to foreign buyers.

They're also hard to get into. Vice TV's drug correspondent Hamilton Morris was only able capture a now-infamous video report on a Chinese factory because his crew went in with its best customer, New Zealander Matt Bowden, on the pretext of making a music video for Bowden's Starboy character. 

That lab, with its stained walls and grubby open buckets of crystals, was not a pretty sight. But a 2012 study published in the Journal of Analytical Toxicology analysed 140 retail samples and found that: "Toxicity linked to the use of such products is unlikely to be due to impurities present in the raw synthetic cannabinoid preparation. Rather, such toxicity is more likely due to other constituents in the herbal preparations or to the effects of the cannabinoids themselves."

Let's just hop in this time machine here and go back to 2006. Yes, certainly, had natural cannabis been legal before the market developed, it may have developed very differently, or not at all. It's worth noting that one early driver of synthetic uptake was that it did not show up in workplace drug tests.

But California, where the loose medical cannabis regime makes natural cannabis fairly easily available, has still seen problems with synthetics. The state moved to ban the chemicals last year after a rash of overdoses in the "Skid Row" area of downtown Los Angeles. The fact that use of synthetics was higher among the homeless and dispossessed seems significant. This is a population that may prefer the strong dissociative effects of synthetic products to the milder buzz of cannabis.

There are also economic imperatives. Growing natural cannabis is time-consuming, fairly expensive and – where it is illegal – risky. Getting chemicals across borders remains an issue, but once a kilogram of AMB-FUBINACA is landed, it might retail for 500 times what it cost. It’s the same principle that saw bootleggers prefer spirits to beer during alcohol Prohibition in the US.

So freeing the herb might help, but it's not going to be a magic wand.