This is a Vice mini-documentary about homeless people having life problems with synthetic cannabinoids in Britain:
This is an introduction to pharmacodynamics, which explains the difference between full and partial agonists around 7:30:
THC, which we know and love, is a partial agonist of the CB1 receptor. Synthetic cannabinoids are full agonists. If you were to smoke weed until you couldn’t get any higher (saturated CB1 receptors), you could get higher than that with a synthetic cannabinoid. Tolerance and withdrawal are increased correspondingly. It’s debatable whether cannabis withdrawal is intense enough to count as a psychiatric disorder, but the Spice addict in documentary was having issues.
The efficacy is more important than the potency.
A review paper points out the risk of drug interactions, kidney toxicity, and genetic inability to metabolize the drugs:
Mechanistic studies have shown that selective inhibitors of CYP2C9 (sulfaphenazole) and CYP1A2 (α-naphthoflavone) block oxidation of JWH-018 and AM2201 in human liver microsomes (Chimalakonda et al., 2013), further demonstrating the importance of these P450 isoforms in the detoxification of these compounds. The in vitro evidence suggests that individuals with certain allelic variants for these enzymes might be more likely to experience increased toxicity following the use of synthetic cannabinoids. Urinary elimination of synthetic cannabinoids or their metabolites may contribute to the kidney toxicity that has been observed with some of these compounds (Sobolevsky et al., 2010; Moran et al., 2011; Centers for Disease and Prevention, 2013).
Given their shared metabolism via P450 isoforms, combined use of synthetic cannabinoids and various prescription medications may result in adverse drug–drug reactions. Commonly prescribed drugs, such as valproic acid and sertraline potently inhibit CYP2C9, whereas drugs, such as ciprofloxacin and fluvoxamine, strongly inhibit CYP1A2. Additionally, CYP2C9 is a major polymorphic enzyme (Paine et al., 2006) and is responsible for the metabolism of a number of clinically important drugs, such as warfarin, phenytoin, tolbutamide, losartan, and ibuprofen. More than five allelic variants have been identified, including two “loss of function” variants (CYP2C9*4 and CYP2C9*5) (Seng and Seng, 2008). Similarly, CYP1A2 is responsible for the metabolism of numerous psychiatric medications, including olanzapine, clozapine, haloperidol, thioridazine, imipramine, clomipramine, fluvoxamine, and tacrine (Shirley et al., 2003) but is well conserved without common functional polymorphisms (Hiratsuka, 2012). Hence, the possibility of drug–drug interactions is a serious consideration using synthetic cannabinoids.
This paper points out that Spice, K2, etc. don’t contain CBD, and that probably has something to do with why they tend to produce more “adverse psychiatric side effects” than smoking weed. It matters what you’re smoking:
METHOD: A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.
RESULTS: Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.
Summing up the situation: The government banned marijuana, with the express purpose of making it more expensive. It pursued social and economic policies that caused there to be lots of homeless mentally ill people. Those people are suffering human beings seeking relief for themselves. They like to smoke weed, but justifiably fear police persecution. Picking the lesser of two evils, they do something about their suffering, except it’s a whole lot worse than smoking weed would’ve been. Weed has many good things about it, not least of which is the absence of of kidney toxicity.
People like smoking weed, and prefer it even in the middle of a Spice addiction. If nobody were arresting or drug testing them for it, they’d just get high like people have been doing since ancient times.
Social policy designed by sadists produces bad outcomes. Who knew?