Modern Canna Cannabis Classifications

By: Hannah Grzech

“Fake weed,” “synthetic cannabis,” “herbal incense,” or whatever name tickles your brain, synthetic marijuana is anything but real marijuana. These commonly used names are the first red flag when it comes to these products because they are complete misnomers. These “designer” drugs are called new psychoactive substances (NPS), which are unregulated mind-altering substances that are made available to the public to mimic the effects of illegal drugs. The synthetic cannabinoids in “fake weed” are man-made psychoactive chemicals mixed with solvents and sprayed onto plant material like herbs to appear as cannabis. They also come in liquid form for devices like vapes and mixed into edibles to be more appealing to younger generations. Then, they are conveniently sold at corner stores, gas stations, and online in colorful packaging under fun brands such as K2, Spice, Scoobie Snacks, Black Mamba, Bombay Blue, and Green Giant. 

Image Credits: Office of Addiction Services and Supports

How Synthetic Marijuana Works

The psychoactive chemicals in natural marijuana that produce a “high” are cannabinoids, notably Delta 9 THC and CBD. Synthetic cannabinoids are produced in a laboratory and then referred to by a plethora of misleading names. They have no natural source, therefore they can be drastically inconsistent in their chemistry and effects. More accurately, these drugs should be called synthetic cannabinoid receptor agonists (SCRAs). SCRAs are meant to mimic natural THC by acting on the same brain cell receptors. This is where the endocannabinoid system comes into play. Basically, your body contains cannabis-like molecules called “endocannabinoids,” which bind to CB1 receptors in the brain and CB2 receptors in the digestive and immune systems. When THC binds to the CB1 receptors, it overwhelms the system and produces different effects from feeling calm and relaxed to producing anxiety, paranoia, and even psychosis. 

Image Credit: Dr. Raimondo Bruno 

SCRAs are even more dangerous compared to those from natural marijuana because they are practically random plants with man-made chemicals that greatly vary in chemical composition, unknown additives, and potencies. Since THC is only a partial agonist and SCRAs are full agonists, they have a higher affinity for the CB1 receptors and bind harder to produce stronger effects. One of the earliest psychoactive compounds found in SCRA drugs, JWH-018, has four times the affinity for CB1 receptors and 10 times the affinity for CB2 receptors than THC. Many SCRA products have been found to have potencies 10-100 times that of natural marijuana resulting in dangerous, unpredictable side effects. The 2016 “zombie” outbreak in a New York neighborhood was a mass intoxication of 33 people due to “AK-47 24 Karat Gold.” Victims exhibited blank stares, groaning, and slow mechanical movements of their limbs from this strong depressant found to be 85 times more potent than THC. 

Synthetic Cannabis Addiction

One common misconception about cannabis is that it is a safe drug. Anything capable of producing psychoactive effects can be very dangerous, especially when its production and distribution is unregulated. SCRAs are ultra-potent with evolving formulas and long half-lives that can result in prolonged psychoactive effects. This can lead to severe intoxication, addiction, disrupted neurodevelopmental processes, psychosis, serotonin syndrome, and death. Cannabinoids interact with the body’s reward system through endocannabinoid signaling to induce the release of high levels of dopamine leading to addiction. Since SCRAs fully bind to the endocannabinoid receptors, the effects on the reward system are even stronger. Additionally, there are often other addictive substances such as nicotine added to purposely create consumer dependency and build a steady demand to increase profits. Without any sort of regulation of SCRAs, manufacturers are free to control the market in this way. 

Image Credit: Evolution of Synthetic Cannabinoid Structures

More Weed Is Not Always Better

Chronic use is associated with developing tolerance as one’s body gets used to the chemical levels and then demands more to experience the same “high.” This leads to increasing doses just to get through the day and further risking the chance of overdosing. It is very difficult to overdose on natural marijuana, whereas it’s much more common for synthetic marijuana because products can greatly vary between batches. Overdoses are a medical emergency and signs include stroke, seizures, heart attack, hallucinations, suicidal ideation, acute kidney failure, and unconsciousness. The effects on each individual are different based on genetic predispositions, drug interactions, mental health, and even environment, so the chances of a “bad high” and overdose are very unpredictable.

Synthetic Weed Can Be Dirty

Determining the pharmacological effects of SCRAs is inhibited by the presence of various adulterants including nicotine, caffeine, harmaline, oleamide, and opioids. There’s the possibility of undetectable compounds blended into products to enhance effects, potency, weight, or volume to ultimately increase profits. Even more than natural cannabis, synthetic cannabis is susceptible to microbial, pesticide, heavy metal, residual solvent, and chemical byproduct contamination due the nature of their synthesis and lack of quality control before reaching consumers. In 2018, there were 255 cases of coagulopathy from brodifacoum-laced synthetic marijuana, including 8 deaths. Whether this was caused by cross-contamination or it was deliberately laced with the agent to increase euphoric effect by its slowing metabolism, it managed to be freely distributed across several states.

Image Credit: Iviagora

Recovering From Synthetic Marijuana

Withdrawal symptoms from chronic synthetic marijuana use can be severe from the usual nausea, mood swings, and anxiety to symptoms as intense as heroin withdrawal. One study notes the onset of seizures when a 44 year old chronic user went through withdrawal, while other studies describe hallucinations and psychosis. The majority of our understanding of cannabinoid addiction are from Delta 9 THC studies, but no amount of Delta 9 can stimulate CB receptors to the same degree as high efficacy SCRAs. In that case, SCRA products can’t be viewed as alternatives to cannabis and their unique psychoactive effects need to be recognized when it comes to designing treatment plans for recovering addicts. Development of effective recovery treatment is still in its trial phase and constantly evolving alongside the drugs itself. Targeting the endocannabinoid system in combination with behavioral approaches and psychosocial support seems to be promising. The addition of long-term treatment for any mental health conditions, heart problems, and behavioral or cognitive impairments caused by regular synthetic cannabinoid use is also very important in preventing future substance abuse.

Image Credits: Banyan Treatment Centers

Playing Cat and Mouse With Regulators

If SCRAs are so dangerous, then how are they still available to the public? Since their first emergence in the mid-2000s, they remained completely uncontrolled on any state or federal level until 2010. In 2012, President Obama signed the Synthetic Drug Abuse Prevention Act to permanently name 26 types of SCRAs as Schedule I controlled substances. Each state has since been enacting various regulations and penalties to further control the sale of these products. Unfortunately, it’s a never ending battle because manufacturers can make small changes to the chemical formulas to maneuver around these laws by creating new SCRAs that haven’t been scheduled yet. Drug tests fail to keep up with these ever-changing chemical compositions so they easily go undetected until people are hospitalized or dead. Dealers’ label products “not for human consumption” to avoid advertising them as “synthetic drugs” to circumvent sale restrictions. The law eventually puts regulations on labeling and branding to quickly ban individual substances. This is where the problem lies; New SCRAs exist in a gray area until the law catches up since drug prohibition laws essentially set the “battle lines” for manufacturers to ultimately outsmart on little technicalities with the endless possibilities of chemistry and the limitations of legislation. 

Image Credits: Katharina Bucholz

Hope for the Future

Due to these limitations, alternatives to prohibition and further criminalization have been enacted by states. In an approach to reduce drug-related accidental deaths and protect public health, they are providing outreach and resources to vulnerable populations in addition to comprehensive education of emerging substances to youth. States are revisiting plans to tax and regulate natural marijuana in hopes of reducing the demand for “legal alternatives” like SCRAs. This decline in popularity has already been seen in states that have legalized medical and recreational marijuana in recent years. The Poison Control data reveals that SCRA exposures have dropped from 7,792 in 2015 to only 313 as of July 31st, 2022. After examining 7,600 SCRA-related calls between 2016 and 2019, researchers discovered that states with legal recreational cannabis had 37% fewer poisoning reports than those with restrictive policies. It appears that users who have the choice of a less toxic product would potentially do so. The study ultimately points to the importance of a regulated adult cannabis market which includes proper testing, labeling, and packaging to decrease potential consumer harm. 

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