A previous post was about terpenes in marijuana smoke that complement or counteract the effects of THC. They mostly act at places other than cannabinoid receptors: acetylcholinesterase (pinene), alpha2a adrenergic receptors (myrcene), 5-HT1A receptors (limonene), etc.
Beta-caryophyllene is special because it’s a CB2 agonist. It was under-appreciated for a long time, but CB2 receptors are expressed all over the brain in addition to the immune system. It’s sort of presumed that CB2 agonists are “non-psychoactive,” but CB2 receptors clearly regulate behavior. Mice without CB2 receptors are sad and afraid:
A CB2 agonist promotes neurogenesis, and CB2 agonists upregulate 5-HT2A receptors in prefrontal cortex (good or bad?). Beta-caryophyllene in particular has antidepressant and anxiolytic effects mediated by the CB2 receptor.
The story with CB2 receptors and addictive behavior is a bit more complicated. Beta-caryophyllene has anti-alcoholism effects in mice, although this implies the opposite. Another CB2 agonist antagonizes the effects of cocaine, but tonic CB2 activity seems to play a role in cocaine-induced (but not cue-induced) reinstatement of cocaine seeking (also see this). The rewarding properties of nicotine depend on CB2 receptors.
In the rest of the body, CB2 receptors suppress pain and inflammation (which are obviously related to stress and depression). You can find beta-caryophyllene in well-known cannabis strains like Trainwreck and Sour Diesel.
Of course, you can also find it in black peppercorn. Apparently, Neil Young advised Howard Stern that he should eat 2-3 peppercorns when he started getting The Fear. They knew about pepper all the way back in 77 AD. From Russo’s terpene review:
The gelotophyllis [‘leaves of laughter’ = cannabis] grows in Bactria and along the Borysthenes. If this be taken in myrrh and wine all kinds of phantoms beset the mind, causing laughter which persists until the kernels of pine-nuts are taken with pepper and honey in palm wine.
He meant black pepper. It probably couldn’t hurt to chew peppercorns all the time. If you did, you’d also be ingesting an alkaloid called piperine. Piperine has lots of good things about it.
Piperine counteracts the effects of chronic unpredictable mild stress (and corticosterone) in a BDNF-dependent fashion. That is, piperine and beta-caryophyllene are both likely to be antidepressant, for the same reason as other things known to be antidepressant.
Xanax is a typical drug you’d use to treat anxiety. Benzodiazepines bind at the aptly-named “benzodiazepine site” on GABA-A receptors. Drugs can stick to receptors in multiple places, not limited to where the natural neurotransmitter would go. This is called “allosteric modulation,” and it’s something CBD does to opioid receptors. Benzodiazepines (and alcohol) are great at relieving anxiety, but they suck in terms of being good life directions. Piperine modulates GABA-A receptors, but not at the benzodiazepine site. This would be anxiolytic in the short term, complementing the long-term antidepressant (rather than life-ruining) effect.
Piperine complements other drugs in general by slowing metabolism and increasing bioavailability.
This is someone’s firsthand experience with piperine:
In combination with Methylphenidate it seemed to exhibit some stimulating effects, which were overall significantly stronger than the ones of MPH itself, but again somehow weird. On it’s own (due to extensive use of multiple drugs at this time has just a limited meaning – but most other drugs should have had just a minor effect) it had some weird effects which were somehow sedating. I tried it in very different settings again, but the effects seemed to vary greatly and most likely depend strongly on the different plasma levels of other substances.
But anyway i wasn’t able to assign a well defined profile to it. This sounds strange, but it’s not difficult for me to do with other substances even in combination.
The doses i used ranged from ~100mg to 500mg. At first it was used pure, then just in form of pepper of which the piperine-content was known.
The mix of alerting and calming effects would be consistent with MAO inhibition and GABA-A facilitation. Anyway, I went to the store and bought some black pepper. The placebo effect is the worst that could happen, since everybody eats black pepper, anyway. Pretty good vegan cannabinoid product:
“Haha!” I thought, “conservative people have been eating cannabinoids all along, because they smell delicious.” I did a Google image search for “haha guy” and then I saw this:
I was like “I told you so” and they were like “but you’re still a nigger” and I felt really drained and defeated. Maybe I should just go hang out with the Klan and impress them with my essential awesomeness. It worked for this guy IRL, whereas “Death to the Klan” got people killed IRL.
I sat down to write about the pharmacology of pepper, and the internet laughed at me for being black. I hear the ice cream truck all the time:
It’s like being psychotic and voices show up in random places and say bad things about you and nobody else can hear. Or like you’re getting bullied and the teacher pretends to be unaware. Great feeling of futility.