Economist Writing Every Day

Since I have posted on the recreational drugs/painkillers kava and kratom for the past two weeks (here and here), I figured I would round it out with a look at the various active compounds that can be derived from the cannabis plant. I knew of THC (the main psychoactive ingredient in weed) and CBD (very tame), but there are many others. When I visited that head shop/kava bar in Florida last month, I noted that they sold a lot of products containing THC-A, THC-P, and HHC, since THC sale is illegal there:

“Super Looper” Vapes, Containing Cannabinoids

The stork clerk showed me the following road-map (with its color-coded “Measure Your Mellow” legend) of various cannabinoids, taking you from innocuous CBD (“Non-psychoactive, soothes anxiety, anti-inflammatory; calming, relaxing”) to THC-P (“Very psychoactive, best entourage effect; energizing, euphoric, total head and body high”) and HHC-P (“Strongest and longest-lasting psychoactive effect; energizing, sativa-like effect”):

Road-Map of Cannabinoids, with putative effects.

On this roadmap, the main “THC” ingredient in weed is shown as Delta-9 or trans-delta-9-Tetrahydrocannabinol (rated as “Very Psychoactive”).

I don’t want to go too far down this rabbit-hole, but out of curiosity I looked up a few articles to try to understand this zoo of mind-altering compounds. Out of sheer laziness, I’ll start with Wikipedia’s take on the pharmacology, focusing on THC itself:

When THC enters the blood stream and reaches the brain, it binds to cannabinoid receptors. The endogenous ligand of these receptors is anandamide, the effects of which THC emulates. This agonism of the cannabinoid receptors results in changes in the levels of various neurotransmitters, especially dopamine and norepinephrine, which are closely associated with the acute effects of cannabis ingestion, such as euphoria and anxiety. Some effects may include a general altered state of consciousness, euphoria, relaxation or stress reduction, increased appreciation of the arts, including humor and music, joviality, metacognition and introspection, enhanced recollection (episodic memory), and increased sensuality, sensory awareness, libido, and creativity.  Abstract or philosophical thinking, disruption of linear memory and paranoia or anxiety are also typical. Anxiety is cannabis’s most commonly reported adverse side effect. Up to 30 percent of recreational users experience intense anxiety and/or panic attacks after smoking cannabis….Cannabidiol (CBD), another cannabinoid found in cannabis, has been shown to mitigate THC’s adverse effects, including anxiety.

Cannabis produces many other subjective effects, including increased enjoyment of food taste and aroma, and marked distortions in the perception of time. At higher doses, effects can include altered body image, auditory or visual illusions, pseudohallucinations, and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to acute psychosis and dissociative states such as depersonalization and derealization.

Regarding some other cannabinoids:

There are similar compounds in cannabis that do not exhibit psychoactive response but are obligatory for functionality: cannabidiol (CBD), an isomer of THC; cannabivarin (CBV), an analog of cannabinol (CBN) with a different side chain, cannabidivarin (CBDV), an analog of CBD with a different side chain, and cannabinolic acid. CBD is believed to regulate the metabolism of THC by inactivating cytochrome P450 enzymes that metabolize drugs; one such mechanism is via generation of carbon monoxide (a pharmacologically active neurotransmitter) by upon metabolism of CBD.[14] THC is converted rapidly to 11-hydroxy-THC, which is also pharmacologically active, so the euphoria outlasts measurable THC levels in blood.

Almost none of these psychoactive compounds are present in the raw cannabis plant. The raw plant contains THC-A, which is then converted to THC and CBD, etc., by heating (e.g. by the heat of burning the dried leaves in a joint, or by baking in brownies). THC-A itself seems to have some attractive anti-inflammatory properties. This NIH article has a listing of the major classes of cannabinoids along with a description of their chemistries. Various synthetic cannabinoids have also been created, with some them now included in pharmaceutical preparations. I have not dug into all the research, but it seems likely to me that some combination of these other cannabinoids might have more favorable effects than plain old THC.

Although CBD is not itself psychoactive, it appears to helpfully modulate the effects of THC, and to have its own useful properties.  It is used to treat seizures, and possibly anxiety and chronic pain. It can be eaten (think: gummy bears) or applied in skin patches (for longest-lasting, controlled exposure) or oils or lotions. Some varieties (e.g. “Full-Spectrum”) of CBD contain traces of THC, and so act more strongly.

Taking cannabinoids via a tincture under the tongue (where it can cross a mucous membrane, into the bloodstream) takes longer than smoking to show effects, but they last longer. It also gives a more precise dosage, and avoids smoke inhalation, so this seems like a preferable route if it is available. I recall reading some months back that a mixture of THC and CBD taken sublingually was effective in controlling pain. Eating cannabis, as in “Colorado” brownies, can be problematic: it often takes several hours to take effect (via liver metabolism), so users get impatient and start eating more brownies, and then end up way higher than intended.

Long-term adverse effects of cannabis are controversial. Some researchers claim there are none, but:

There is evidence that long-term use of cannabis increases the risk of psychosis, regardless of confounding factors, and particularly for people who have genetic risk factors. A 2019 meta-analysis found that 34% of people with cannabis-induced psychosis transitioned to schizophrenia. This was found to be comparatively higher than hallucinogens (26%) and amphetamines (22%).

Long-term cannabis users are at risk for developing cannabinoid hyperemesis syndrome (CHS), characterized by recurrent bouts of intense vomiting and abdominal cramping during or within 48 hours of heavy cannabis use.

Also, a very recent large study found that 63% of long-term heavy cannabis users had significantly reduced brain function for working memory tasks. (I’ll add that I know someone whose trajectory very strongly suggests that exposure to weed in early teens put a permanent crimp in her mental and emotional functioning).

It seems that habitual use of cannabis can result in general “chill” lassitude, which lowers productivity. As one counselor told a friend of mine, “It is true that with weed ‘nothing happens.’ That is just the problem.”

Weed has long been touted as an alternative pain-killer. I know of people who claim benefits here. Most states allow “medical marijuana” for conditions such as chronic pain or nausea. However, its use is still unlawful at the federal level, so weed must be grown in-state and not transported across state lines.

This NIH site summarizes many studies on cannabis for pain. The evidence is very mixed. Often a significant fraction of subjects report improvements, but so do those on placebos.

My totally amateur takeaway from this flyover: THC and related cannabinoids have a variety of effects on the mind, mostly pleasant but sometimes bad or very bad. There seems little evidence for adverse effects of weed on the body (outside of the brain), but real dangers of messing up your brain with heavy or extended use. As usual with these recreational drugs, harmful interactions are very likely if other substances are used at the same time.

As for pain treatment, it’s effectiveness seems to vary a lot among individuals. Weed may be worth a try as an alternative to opioids, but it still carries significant dangers

If I had to pick a poison for myself as alternative painkiller, at this point it would be a tie between weed (which messes with your brain, not so much your body), and kava (whose side effects mainly show in body parts like the liver and the skin, plus brief nausea). I would experiment to see what worked for me. But first I would make every effort to treat pain through some other means. There are many possible treatments for pain which may be safer than cannabis, and new treatments keep coming. For instance, a friend with neuropathy told me that he experienced relief with a new medicine called Neuropaway.

Huge Disclaimer: I have no expert knowledge here. Don’t act on anything here. All I have done is summarize a few articles. Consult your doctor before doing anything.

P.S.

I could not resist taking a look at the side-effects of drinking alcohol. After all, we all do it, and we have all seen headlines claiming health benefits of drinking a glass of red wine a day. Well, the medical community is pretty down on drinking, saying the proven harms far outweigh the few, slight proven benefits. Even “moderate” consumption can overtax the liver, which really damages it, per this.