Marijuana for Pain

Photo by Jose Luis Sanchez Pereyra on Unsplash

The most interesting & controversial plant in the world.

Marijuana is allegedly medicine, widely believed to be good for insomnia, anxiety and other mood disorders, and — this is a big one — pain.1 As legalization spreads around the world like a wildfire, so does the hype, racing way ahead of the science. It’s a gold rush, and a rare example of a heavily promoted product with a huge target market that isn’t cynical about it at all: millions of shut-up-and-take-my-money customers, millions who don’t need to be convinced of anything, because they already (passionately!) believe that cannabis is essential to their health and well-being.

But countless more potential customers have concerns and questions, and are as cynical about cannabis as they are about vitamins and supplements.

Not everything popular is safe, believe it or not, and some safety issues are emerging as usage surges. Just like conventional pain meds, there are risks. And while the science of pot as a pain treatment is promising from some angles, it’s also incomplete and contradictory. Do cannabis products actually help? The short answer is maybe a little,2 and it’s a lot less clear than it should be for a new kajillion-dollar industry.

And there is no such thing as a “broad spectrum” pain killer — it is impossible in principle. Pain is a beast with many heads, and it is impossible to slay them all with the same sword — a point this website goes on and on about. Not much actually works,3 because pain is weird.

Duuuude… so does weed, like, help pain? Or what, man? What was I just talking about?

The cannabasics

Cannabis is a plant, most notably marijuana (bred for its narcotic effects) and the major strain of hemp (bred for other purposes). It’s one of the most interesting plants in the world because it produces chemicals with interesting effects, the cannabinoids. The most interesting and famous of those are THC (tetrahydrocannabinol) and CBD (cannabidiol). All cannabis contains THC, CBD, and hundreds of other related compounds, but there’s a lot more THC in marijuana plants, and a lot more CBD in hemp.

Both compounds are alleged to be pain killers, but CBD has barely been studied.

THC gets you high — “psychoactive effects.” It’s a narcotic, and the reason the legality of cannabis is a major issue.

CBD does not get you high — but it’s also not always well-separated from THC.

There’s a difference between any old cannabis (whatever the hell people stuff in their vaporizers or bake into a cookie) and cannabis-based medications (THC and/or CBD extracted from standardized plant sources, purified, and turned into something a little more predictable).

Are cannabinoids pain killers? “It’s complicated”!

As a science journalist, I am honour bound to emphasize that cannabinoids are not proven pain-killers. “Proof” is a high bar that has not yet been cleared.

Importantly, cannabis doesn’t actually need to be scientifically “proven” to be worth trying for desperate patients. It is safe enough, even if it isn’t quite as safe as everyone wants to think (see below). But it is not evidence-based medication for any kind of chronic pain, despite the avalanche of such claims.

A huge 2017 review of the scientific literature on cannabis concluded that there is “substantial evidence that cannabis is an effective treatment for chronic pain in adults.”4 But the review also explains that the evidence shows only modest benefits so far, there is uncertainty about every detail, and significant practical problems abound for both researchers and consumers:

“Very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products.”

And that’s the more optimistic take.

Other reviews of largely the same evidence have been much less optimistic. In 2017, Nugent et al looked at 27 scientific trials of cannabis for chronic pain trials, and were disappointed: their conclusions were barely positive for neuropathic pain, and just inconclusive otherwise.5 In 2019, Häuser et al wrote:6

“The more detailed the search of literature and the higher the criteria of the inclusion of studies and of the clinical relevance of the study findings, the more disappointing are the conclusions of systematic reviews on the efficacy and safety of cannabis medicines. … Cannabis medicines can be regarded to be third-line therapy for chronic neuropathic pain. There are signals of a lack of efficacy for all other chronic pain syndromes.”

You are harshing our buzz here, Häuser et al! (The cannabis jokes practically write themselves.)

A 2022 review concluded that most of the benefit reported by other studies is attributable to placebo — and (weird angle) they also concluded the studies that got the most media attention were the most likely to perpetrate “an overestimation of the effectiveness of medical cannabis.”7

How about cannabis for fibromyalgia, a condition defined by pain? If cannabis is good for pain, it almost has to help these patients, surely? Unfortunately, the science on that barely exists at all.89 But there’s not *nothing*, and the existing evidence consistently reports “small” effects … at best.10

A noteworthy new trial of CBD for acute back pain

Studies of pure CBD for pain remain rare, which makes a good 2021 Australian trial noteworthy.11 Researchers tested CBD in the same situation where doctors might normally prescribe powerful anti-inflammatories or opioids: in people who have gone to the emergency room with severe back pain. A hundred patients were given an ibuprofen and paracetamol plus either 400mg of CBD or a bogus pill that looked just like it.

This a fair test in several ways. If CBD actually has anti-inflammatory properties, the people who got a CBD booster should certainly have gotten some extra relief. Severe acute back pain is a tough pain-killing challenge, but we should expect anything touted as “good for pain” to help out at least a little in this situation.

Unfortunately, CBD made no difference at all: it was like it wasn’t even there. •sad trombone• The groups were identical on all outcomes: pain levels, how long the patient stayed, the need for “rescue analgesia” (the Oxycodone), and adverse events.

It is conceivable that CBD alone, or repeated doses, would have performed at least as well as standard meds, and maybe more safely — safer than NSAIDs anyway12 — but it’s a long shot. This was quite a fair test, and CBD just bombed.

So many studies, so little good science

Why does everyone think there’s so much evidence that cannabis treats pain? Because it’s easy to mistake quantity for quality. When you want to believe in something, a buttload of lame studies on PubMed look like a gold mine of “promising” hard data. Unfortunately, modern science is badly polluted with huge numbers of bad studies — especially about hot topics like this. This trickles down to popular writing on the topic.13

And it floods into advertising. We can also thank a huge new industry for their profit-motivated multi-year campaign to advertise cannabis, which invariably touts it as evidence-based, loudly and creatively — all without much regard for the truth. They have an empire to build.

Fortunately, not everyone is careless with their citing. Dr. Bronnie Thompson, a New Zealand occupational therapist, wrote in 2019 that “the evidence is pretty skinny. Lots of studies, yes, but not well-conducted or reported, and the change in pain intensity is small.” Cannabis and cannabinoids for persistent pain? (There’s a more detailed and most excellent rant later in her article, highlighting many problems.14)

“A promising treatment is often in fact merely the larval stage of a disappointing one. At least a third of influential trials suggesting benefit may either ultimately be contradicted or turn out to have exaggerated effectiveness.”

Bastian, 2006, J R Soc Med

CBD versus THC for pain

CBD for pain has barely been studied — almost all the science (such as it is) is about THC or a THC+CBD combo. And yet the hype about CBD has been so intense that it’s clearly now a widespread belief that CBD is good for pain — even though we really have no idea. Despite the relatively widespread use of CBD, we don’t even have “good” anecdotal evidence (to the extent that any anecdotal evidence is useful at all). Not many people have much experience with pure CBD — it remains relatively obscure.

Once again, THC is intoxicating and CBD is not. THC might give you the giggles, and CBD never will. Most people cannot even tell that they’ve taken CBD! CBD is also easier to obtain and use: it’s probably even safer, it doesn’t blow your mind, it can be used topically, and its legal status is less problematic.15

Unfortunately, the pain-killing powers of CBD are just as ambiguous as THC,16 if not more so. In fact, not only is CBD downright underwhelming for pain, CBD products are so poorly regulated that dosages, contamination, and adulteration are all real concerns. A 2023 scientific review not only found virtually no evidence of efficacy, but signs of liver toxicity, probably due to contaminants17 and/or by messing with other drug effects.18

You’re always rolling the dice a little with vitamins, supplements & medicinal plant products like cannabis: it’s the wild west out there, these products are poorly regulated in most places & the dosage of active ingredient is only the least of the concerns.

The psychoactive effects of THC may be highly relevant to pain-killing, because psychology is relevant to many kinds of pain.19 And THC may function as a muscle relaxant, another way that THC might be relieving pain indirectly. More about the clinical relevance of psychoactive effects later on.

Hype and hope (at an unprecedented scale)

The growth of the cannabinoids industry is bonkers as legalization spreads, and that industry has begun to aggressively advertise their product based on the alleged benefits — knowing full well that a very large percentage of their target market already believes their message, or (crucially) wants to believe it. An ad man’s wet dream.

The science doesn’t match the marketing, of course. Does it ever?

Sometimes you just need a bullshit detector.

Seen in a Vancouver train station. Someone is spending a lot of money on piquing curiosity! The website, EndoHelp.ca, is a lot of nothing about your “endocannabinoid system.” This looks like a costly campaign with a science-y website whose ultimate purpose is to sell weed — a perfect example of the marketing-powered hype.

But the hope is extraordinary. People believe in the power of cannabinoids more passionately than any other widely used pain treatment I can think of — which is really saying something. At times, their enthusiasm leads them to reach way beyond their own knowledge and the evidence and into zealotry. Not cool! Counter-productive.

These people are not all wrong about their own experience (obviously), but they aren’t exactly unbiased either. There are many ways that cannabis could convince fans that it’s effective without actually having a reliable, measurable pain-killing effect on the average person. A drug that makes people euphoric, for instance, is bound to have loyal fans regardless of anything else…

Killing pain versus coping with it

There’s a difference between reducing pain and simply being so baked that you care less about being in pain. The psychoactive effects of THC may be the only thing that makes it “good for” pain. Good for suffering less. (And another reminder: pure CBD has no psychoactive effects, and is barely studied for its effects on pain.)

If you’re experiencing pain that doesn’t go away, feeling good is such a contrast to what you’re feeling most of the time, I wonder if this explains some of the effect.

Dr. Bronnie Thompson, Cannabis and cannabinoids for persistent pain?

Much ink has been spilled about how badly humans want to suppress and alter their consciousness. The 2020 film Another Round is based on the idea that humans can just barely cope with life without alcohol,20 and we’d be better off if we were tipsy all the time.

But why “pick your poison” when you can pick a psychoactive substance that isn’t a poison? There is a strong case that being a little bit high is a much better choice than being a little drunk — more pleasant, fewer side effects, and much less poisonous. Alcohol is actually poisonous — every dose stresses our liver. Pot ain’t perfect, but it’s dramatically safer than booze.

Being human can be rough, and arguably chronic pain is as shitty as it gets. If there is the slightest truth to the claim that warping our minds is a critical coping strategy, then THC must be “good for” pain in that sense at least. Just as long as we’re clear that it’s not the same thing as “killing” pain.

Paranoia and anxiety: not all psychoactive effects are good!

Anxiety has a significant role to play in chronic pain in many ways, and so anything that suppresses it can be considered helpful for pain. Cannabis has a strong undeserved reputation as an anti-anxiety medication.

People think of pot users as “mellow,” and that is probably mostly what leads to the assumption that cannabis is good for anxiety.21

But “paranoia” is an extremely common side effect, and it’s basically synonymous with anxiety. THC especially probably aggravates anxiety in many patients in both normal use and in withdrawal (more below) — it can get you both coming and going. If THC is helpful for pain, it’s probably not because it eases anxiety. The science is very limited, however, and the reality is that it can probably swing either way, either reducing or increasing anxiety.22 I go into a little more depth in another article: Anxiety & Chronic Pain: A self-help guide for people who worry and hurt.

Usage guidelines for beginners

If you’re new to marijuana, there’s a bit of a learning curve. Here are some tips:

• Pure topical CBD creams and oils are overall the safest and most convenient, so they should probably be your first priority to try. CBD pills or edibles are also good option to investigate, but note that they can contain THC. And although THC may be more effective, that’s also where that learning curve is steepest.
• Use caution with THC edibles! Dosing and duration of effect are huge wildcards. You can get way, way too high for comfort. There’s no major danger short of extremes, but people can be so incapacitated and freaked out that they end up in the ER.
• Avoid vaporizers that use oil infused with cannabinoids, due to scandalous, tragic safety issues because asshole manufacturers have added other dangerous, un-tested substances23. Dozens of people died in 2019. Died!
• Infused oils aside, vaping raw cannabis in moderation is quite safe.24 Just take it easy for at least your first three times — just one or two modest inhalations of vapour is just fine to start.
• Please don’t smoke the stuff — smoke is hard on the lungs no matter what you are burning.

What could possibly go wrong? Risks and harms of cannabis

The legend: cannabis is completely harmless.

The reality: nothing is completely harmless. Yes, cannabis is dramatically safer than alcohol.25 But it is definitely not completely harmless.

Most prominently, the dosage-control problem with edibles is very real. It’s hard to effectively study, regulate, or treat anything with a molecule if the dosage is tricky to control and regulate. It also makes it harder to avoid overdose. Typical overdose isn’t dangerous, but is extremely unpleasant.

“Cannabinoid hyperemesis syndrome” — episodes of severe nausea and violent vomiting — is an extremely unpleasant and destructive side effect that seems to be non-rare.

Withdrawal from regular use can cause trouble, especially for chronic pain patients.

The only major safety concern is an on-going controversy about a risk of causing a psychosis (or triggering a vulnerability to it).

Some more about each of those…

THC overdose

Emergency departments have started to fill up with people who are having bad THC trips. For instance, ED visits in Colorado were far higher than expected after legalization of recreational use.26

I have ingested or vaped THC and CBD products since about 2015 when my own chronic pain problems began. I have accidentally overdosed once: I ate about three times my normal nightly dose thanks to some confusion about a change in edible products, and the result was horrendous. For hours, all I could do was moan and writhe. It was terrifying, and the only thing that kept me from calling 911 was my confidence that THC overdose is nearly incapable of causing direct harm.

Cannabinoid hyperemesis syndrome: extreme vomiting

One of the most alarming side effects of THC/CBD is cannabinoid hyperemesis syndrome (CHS): escalating episodes of chills, nausea, and painful projectile vomiting.27 CHS tends to be worse in the morning, and patients often alternate between vomiting and self-treating the chills with hot baths and showers.

How bad is it? Episodes tend to recur with increasing frequency and ferocity over time, and it can get so extreme that dehydration is a serious threat, even lethal — like in the case of Brian Denny, who died that way in 2019, a tragic story told by his mother. Even when it’s not deadly, this condition wrecks lives. Even mild nausea is a hard symptom to live with.

Is it rare? It’s not “common,” but probably “rare” isn’t really the right word either. Many emergency room docs and nurses seem to be familiar with it. Support groups have been multiplying. It’s hard to connect the dots at the best of times, especially when many people don’t want to.

While clinicians and most regular marijuana users regard CHS as a rare condition — if they have heard of it at all — the literature suggests otherwise. Many cases of CHS are likely misdiagnosed or not medically treated at all. … it is possible that 2.75 million Americans suffer from CHS. It is likely many are not even aware that their symptoms relate to their cannabinoid use.28

And syndromes like this are often the tip of a pathological iceberg. For each severe case, there are probably many minor ones,29 and at least some cases (if not many) probably have subtle prodromal phases.30 Which is quite a disturbing possibility. And it also probably isn’t limited to hardcore usage. Clearly high dosage users are at the greatest risk, it’s also not a hard rule. For instance, in Brian Denny’s case:

He was not a daily smoker, and he had been smoking on and off for about 3 years before he developed symptoms. Brian was also experiencing symptoms even after he had quit smoking, which caused us to doubt the diagnosis further.

Is this fear-mongering? If only! But CHS is all-too real. Many cannabis fans deny the existence of CHS, and resistance to the diagnosis can be fierce: some people really don’t want to hear a “discouraging word” about cannabis. It’s easy to make a simplistic case against it because cannabinoids are often used for their anti-emetic properties … but that is the nature of this paradoxical beast, and it’s a common pharmaceutical paradox (many drugs can both treat and cause a symptom in different contexts).

Cannabinoid-Hyperemesis.com has lots of well-presented information about CHS, and is a good place to start if you want more information.

Cannabis withdrawal syndrome: quitting THC can mess with you too (and make pain worse)

The popular view is that THC withdrawal symptoms is almost always minor, and mainly limited to insomnia, but recent evidence suggests a harsher reality.31 A 2020 scientific review of CWS concludes that “cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis” and the symptoms can be substantial. The authors also express the opinion that both cannabis use and withdrawal probably aggravate anxiety, depression, and other psychiatric disorders.

No doubt many cannabis fans will be outraged by this. But it’s consistent with my own experience, and some evidence, I encourage to you to take it seriously.

Cannabis and psychosis: mental meltdowns, especially acute psychosis and schizophrenia

Unfortunately, there is decent evidence that cannabis can break your brain.32 Please don’t mistake my informal language for a cavalier attitude: I have lost two friends to acute psychosis.33 The high stakes make me want to communicate effectively about it (which means using language people can easily relate to).

Most likely the only people at risk are younger, have some underlying vulnerability, and/or are using way too much cannabis. But that doesn’t make it any less serious: most things that go terribly wrong with people involve some kind of vulnerability, and there’s definitely nothing exotic about being young and having a brain that’s still growing.

Nevertheless, the risk for healthy adults using cannabis non-recklessly is probably extremely low to nil.

The link between cannabis and psychosis and other psychiatric dangers is controversial: we have data that suggests a correlation, but not causation.34 But correlation can be an awfully good hint.35

My own experience with CBD and THC for pain

Bupkis, nowt, zilch, nix, bugger all, sweet Fanny Adams, nada, naught.

I am a chronic pain patient myself. And my pain, while still unexplained, is quite neuropathic in character — the type of pain allegedly most susceptible to cannabinoids. Alas, not in my case. CBD is particularly useless. THC is more complicated. It hasn’t had any obvious direct pain-killing effects. I have just as many weird aches and zings when I’m high as when I’m not. But perhaps I have benefitted indirectly from the psychotropic effects.

THC doesn’t make me euphoric, and hasn’t for years. No giggle fits for this guy. I just get anxious or sleepy… and I have to be quite careful with that fork in the road.

If I go to bed anxious, larger doses of THC will make it much worse, not better. THC absolutely does not calm me down. Smaller doses are usually okay, and when I am already feeling peaceful, larger doses are excellent for my sleep. In that one way, I can say that THC is good for my pain: it helps me sleep, some nights, and that’s invaluable, because poor sleep is a top pain pisser-offer. Anything that helps with sleep is effectively a pain medication for me.

But I really do have to be cautious, or it will backfire badly, and those nights are just the worst.

About Paul Ingraham

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter., or subscribe:

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Related Reading

Related topics around PainScience.com:

• Anxiety & Chronic Pain — A self-help guide for people who worry and hurt
• The Insomnia Guide for Chronic Pain Patients — Serious insomnia-fighting advice from a veteran of the sleep wars
• A Rational Guide to Fibromyalgia — The science (and not the pseudoscience) of the mysterious disease of pain, exhaustion, and mental fog
• Chronic, Subtle, Systemic Inflammation — One possible sneaky cause of puzzling chronic pain
• Sensitization in Chronic Pain — Pain itself can change how pain works, resulting in more pain with less provocation
• Other kinds of pain medications:
  • The Science of Pain-Killers — A user’s guide to over-the-counter analgesics like acetaminophen, ibuprofen, and more
  • Voltaren Gel: Does It Work? — The science of the topical pain-killers, which can be effective without dosing your entire system
  • Vitamins, Minerals & Supplements for Pain & Healing — Critical analysis of most popular “nutraceuticals” — food-like pseudo-medicines taken for medicinal purposes, especially glucosamine and creatine, mostly as they relate to pain, arthritis, and recovery from exercise and injury
  • Opioids for Chronic Aches & Pains — The nuclear option: Oxycontin, codeine and other opioids for musculoskeletal problems like neck and back pain
  • Does Epsom Salt Work? — The science and mythology of Epsom salt bathing for recovery from muscle pain, soreness, or injury
  • Vitamin D for Pain — Is it safe and reasonable for chronic pain patients to take higher doses of Vitamin D? And just how high is safe?
  • Does Arnica Gel Work for Pain? — A detailed review of popular homeopathic (diluted) herbal creams and gels like Traumeel, used for muscle pain, joint pain, sports injuries, bruising, and post-surgical inflammation
  • Homeopathy Schmomeopathy — Homeopathy is not a natural or herbal remedy: it’s a magical idea with no possible basis in reality
  • Muscle Relaxants — This topic is covered in several of my books in detail — low back pain, neck pain, trigger points, frozen shoulder, headaches. There is also condensed (but free) information about them in Cramps, Spasms, Tremors & Twitches.

More about cannabis around the web:

CBD for chronic pain: The science doesn’t match the marketing, by Shafik Boyaji, MD for Health.Harvard.edu.
• Medical marijuana as the new herbalism, part 1: Science versus the politics of weed in New York and beyond and Part 2: Cannabis does not cure cancer, by Dr. David Gorksi for ScienceBasedMedicine.org
• Medical Marijuana: Where is the evidence? Marijuana is widely touted as an effective medicine for an array of conditions. But what does the evidence actually tell us? by Scott Gavura for ScienceBasedMedicine.org.
• Marijuana Beliefs Outstrip Evidence, by Dr. Steven Novella for ScienceBasedMedicine.org. “There is a lot of hype surrounding medical marijuana, but the clinical science is very preliminary. The risks and benefits have not been researched enough to make science-based recommendations.”
• If Cannabis Should Meet Fibromyalgia, by Dr. John Quintner for FMPerplex.org.
• Examine.com’s cannabis page (extremely thorough evidence review).

Notes

1. Kosiba JD, Maisto SA, Ditre JW. Patient-reported use of medical cannabis for pain, anxiety, and depression symptoms: Systematic review and meta-analysis. Soc Sci Med. 2019 07;233:181–192. PubMed 31207470 ❐

   “Meta-analytic results indicated that pain (64%), anxiety (50%), and depression/mood (34%) were common reasons for medical cannabis use.”

   Sleep is in the mix, and more popular with older adults, but it doesn’t compete with the numbers for pain, anxiety, and mood.

2. NationalAcademies.org [Internet]. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research; 2017 Jan [cited 21 May 4]. PainSci Bibliography 53746 ❐

   This massive review of the scientific literature on pot concludes that there is “substantial evidence that cannabis is an effective treatment for chronic pain in adults,” but there are major caveats. More references to come, including more pessimistic reviews like Nugent 2017 and Häuser 2019.

3. The pain system is an extremely basic physiological system, so thoroughly tangled up with other critical systems that it is extremely hard to blunt pain without major side effects. Trying to “kill” only pain is like trying to kill trees without hurting the forest. Anaesthesia is the only truly reliable way to kill pain, because it stops almost everything else too! THC suppresses/alters consciousness like a kind of pseudo-anaesthesia, which might account for THC’s reputation as a pain-killer! But it may only work in rough proportion to how consciousness-disabling it is … which isn’t a great trade-off.

   For the most optimistic perspectives possible for a skeptic, see What Works for Chronic Pain? A skeptical roundup of all the disappointingly small selection of effective chronic pain treatments (or the least bad ineffective ones).
4. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research 2017, op. cit.
5. Nugent SM, Morasco BJ, O’Neil ME, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Aug. PubMed 28806817 ❐

   This review of 27 scientific trials of cannabis for chronic pain trials is disappointing: weakly positive for neuropathic pain, and just inconclusive otherwise, with some evidence of risks of short term mental fog, car accidents, and psychosis. This conclusion is at odds with other recent reviews and reports, which have offered more optimistic interpretations of mostly the same evidence (most notably The Health Effects of Cannabis and Cannabinoids).

   In addition to finding very little benefit for pain, the review also reports some evidence of risks of short term mental fog, car accidents, and psychosis.
6. Häuser W, Petzke F. [Evidence of the efficacy and safety of cannabis medicines for chronic pain management: A methodological minefield]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2019 Jul;62(7):836–844. PubMed 31139839 ❐
7. Gedin F, Blomé S, Pontén M, et al. Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Nov;5(11):e2243848. PubMed 36441553 ❐ PainSci Bibliography 51397 ❐

   This review of cannabis-for-pain studies found that “placebo contributes significantly to pain reduction” … with not so much contribution from the cannabis itself.

   Translation: THC is not the active ingredient for what little pain relief there is to be had.

   Interestingly, they also reported that study results hyped by the media are the most likely to be the most illusory — the most attributable to placebo — probably because of poor blinding.

   Blinding or masking is all about keeping study subjects from knowing if they are getting a sham as members of the control group, or getting “the good stuff.” (If you hide their status from the researchers too, that’s double blinded.) Blinding is a key feature of a fair test, but full of gotchas, and “some placebo-controlled cannabis trials fail to ensure correct blinding which may have led to an overestimation of the effectiveness of medical cannabis.” There are many ways to botch blinding, but one of the main ones here is that — shocker! — it turns out people can tell the difference between real and fake marijuana! 🤣

   The authors explain their work for a general audience quite nicely in this short article.

8. Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul;7:CD011694. PubMed 27428009 ❐ PainSci Bibliography 52139 ❐

   This is a 2016 review of… hang on a sec, am I reading this right?•rubs eyes, blinks• Just two trials? Oh dear. Two small trials of 32 and 40 subjects. I have never seen a review of just two trials before, but I suppose it’s technically the minimum to be considered a review!

   Both studies used nabilone, which is a synthetic cannabinoid. The results were rotten: it didn’t work, and it had a lot of side effects: “We found no convincing, unbiased, high quality evidence suggesting that nabilone is of value in treating people with fibromyalgia. The tolerability of nabilone was low in people with fibromyalgia.”

   Alrighty then! For whatever it’s worth.

   The actual story here is that cannabis for fibromyalgia hasn’t really been studied. (Nabilone barely counts, even if it was 20 studies.)

9. Kurlyandchik I, Tiralongo E, Schloss J. Safety and Efficacy of Medicinal Cannabis in the Treatment of Fibromyalgia: A Systematic Review. J Altern Complement Med. 2020 Dec. PubMed 33337931 ❐ This 2020 review identified just three randomized controlled trials.
10. Gazendam A, Nucci N, Gouveia K, et al. Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis. Cannabis Cannabinoid Res. 2020;5(4):290–297. PubMed 33381643 ❐ PainSci Bibliography 51932 ❐

    This review of trials of cannabis for acute pain show a “small” effect only — but “statistically significant!” Which is a concept so corruptible and abused that many academic papers have been written begging researchers to stop using it. (The evidence for injected cannabis was a little stronger, but who does that? Interesting if true, useful in some medical contexts, but meaningless to the average person.)

    The distinction between acute and chronic pain is interesting. Cannabis could conceivably be more useful for one than the other, but there’s very little that fails with acute pain but succeeds with chronic.

11. Bebee B, Taylor DM, Bourke E, et al. The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain. Med J Aust. 2021 05;214(8):370–375. PubMed 33846971 ❐
12. Non-steroidal anti-inflammatory drugs (e.g. ibuprofen), are actually quite dangerous — they are hard on the body at any dose. Acetaminophen/Paracetamol, on the other hand, is one of the safest drugs there has ever been at recommended dosages (large quantities are dangerously hard on livers). CBD is likely safer than the former, and likely not as safe as the latter. To be a viable alternative to NSAIDs, it just has to have at least the same effect. But it can’t actually beat acetaminophen on safety, so it would have to be much more effective — and while possible, it seems very unlikely based on this test.
13. Ingraham. 13 Kinds of Bogus Citations: Classic ways to self-servingly screw up references to science, like “the sneaky reach” or “the uncheckable”.  ❐ PainScience.com. 6094 words.

14. I’ve read a heap of papers, and to be perfectly honest, I’m alarmed at the state of the research. Not only are many studies failing to identify the pain mechanisms addressed (neuropathic pain is the most commonly studied, but it’s also common to find studies with mixed cohorts); studies are often short — for a chronic, ongoing problem like persistent pain, we need to have studies carried out over 12 months or more, 8 weeks or less is completely insufficient; the outcome measures used are primarily pain intensity using a unidimensional index like a numeric rating scale – come on guys, pain is NOT a unidimensional problem, and surely we’ve learned from opioid trials that pain intensity isn’t the best outcome measure for a long-term problem? What about participation in life? What about disability reduction? What about sleep? What about reduced use of healthcare? Many of the studies are in rats and mice and last time I checked, I’m not a rat or a mouse, and my physiology is a little different; the analysis of studies is often awful with no mention of dropout rates, no responder analysis, no description of adverse effects and tiny, tiny sample sizes. Worse, the small sample sizes exclude people with comorbid problems like depression, anxiety, insomnia, drug and alcohol use (and yet these are characteristics of many people seeking help for persistent pain). Additionally, most studies don’t indicate whether the people taking part in the study are naive to cannabis – people who use cannabis regularly are less likely to be bothered by adverse effects, so studies aren’t describing what may happen in people who are new to the effects of cannabis.

    I could go on.”

    I bet she can! For whatever my opinion is worth, I completely agree with all of this.

15. Although many jurisdictions still treat it exactly like THC, even though it’s a completely different drug that you cannot get stoned on.
16. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016 Jul;20(6):936–48. PubMed 26517407 ❐ PainSci Bibliography 52794 ❐
17. Moore A, Straube S, Fisher E, Eccleston C. Cannabidiol (CBD) products for pain: ineffective, expensive, and with potential harms. J Pain. 2023 Oct. PubMed 37863344 ❐

    This is an extremely negative review of sixteen studies of CBD for pain.

    “You’ve got to ask yourself one question: Do I feel lucky? Well, do ya, punk?”

    You’ve got to ask yourself that because, in the wacky world of cannabis products, you never quite know what you’re going to get! CBD products are like a game of roulette: you might end up with a little, a lot, or maybe even none of the CBD that’s promised on the label.

    Or is it a game of Russian roulette? Because CBD concoctions also seem to contain a medley of other mysterious chemicals, and they probably aren’t all okay. While verified pure CBD appears to be “largely benign,” trials of commercial products show some evidence of serious side effects, specifically liver stress. That points to toxicity, probably from contamination, but possibly through other mechanisms like adulteration, or interactions with other drugs (see Smith).

    But lots of medications are hard on the liver and the rest of the body, and we routinely accept those trade-offs. Is CBD efficacious enough to justify the risk of a funky batch?

    Probably not. Of the sixteen trials of CBD in various forms, fifteen concluded, “Not today, CBD!” No more pain relief than a good old placebo.

    Many people are quick to claim that they’re just fine with a placebo “as long as it works.” But that rationalization probably cracks under the pressure of liver toxicity.

    “There is no good reason for thinking that CBD relieves pain,” Moore et al. write, “but there are good reasons for doubting the contents of CBD products in terms of CBD content and purity.”

18. Smith RT, Gruber SA. Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions. Front Psychiatry. 2022;13:1055481. PubMed 36704740 ❐ PainSci Bibliography 51638 ❐

    “Given CBD-based products are typically used as edibles, capsules, or sublingual solutions/oils, and since CBD has been identified as the cannabinoid exhibiting the strongest interactions with the CYP450 system, CBD poses considerable risk for drug-drug interactions.”

    The review explores some of the known biology and makes it clear that it’s highly plausible that CBD may exaggerate or suppress the effects of other drugs, but the clinical risks have barely been studied — in a period when usage has grown explosively.

19. Pain is never “all in your head,” but it is often strongly affected by what’s in your head. For instance, back pain is a condition that is notoriously sensitive to what’s going on between your ears. See The Mind Game in Low Back Pain.
20. That premise comes from Norwegian psychiatrist Finn Skårderud.
21. That might be true for some people, but it is definitely not true for everyone. Cannabis is not a sedative, and the appearance of mellowness is mainly due to favourable comparison with alcohol, and the way high people are preoccupied with what’s going on between their ears.
22. Sharpe L, Sinclair J, Kramer A, de Manincor M, Sarris J. Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties. J Transl Med. 2020 10;18(1):374. PubMed 33008420 ❐ PainSci Bibliography 51833 ❐

23. Young, K and Sofair, A. “CDC Reports Breakthrough in Vaping-Linked Lung Injury Investigation.” Nov 9, 2019. Accessed on 2019-11-23.

    Vitamin E acetate has been detected for the first time in the lungs of patients who vaped and developed serious lung injury. Vitamin E acetate is a thick, oily substance added to some e-liquids, particularly those containing tetrahydrocannabinol (THC).

    “These new findings are significant because for the first time we have detected a potential toxin of concern ... from biological samples,” CDC Principal Deputy Director Dr. Anne Schuchat said on Friday. Previously, vitamin E acetate had been detected in product samples.

24. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015 Dec;16(12):1233–42. PubMed 26385201 ❐

    Although we already have many reasons to suspect that cannabis usage is very safe, the more data the better on this topic, and particularly in the context of treating non-cancer pain. The results are good news, and completely consistent with other evidence. Ars Technica:

    Almost every news story one reads about the use of cannabis as a medical therapy contains some variation of disclaimer saying ‘more research is needed’ into the longterm safety of medical cannabis use. Now a tiny bit of that ‘more research’ has been published in the Journal of Pain. The headline result was that there was NO INCREASE IN THE NUMBER OF SERIOUS ADVERSE EVENTS in a group that used cannabis for chronic pain when compared to a group that did not.

    It’s hard to overstate how significant that kind of safety level is for any medication that helps with pain. Even the mildest over-the-counter analgesics come with serious risks (see How risky are NSAIDS?). Cannabis is not risk free — this study did find evidence of non-serious adverse events — but the total absence of serious adverse events is a big deal.

    (By the way, this science comes from Canada, which is where I come from. You’re welcome.)

25. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015 Dec;16(12):1233–42. PubMed 26385201 ❐

    Although we already have many reasons to suspect that cannabis usage is very safe, the more data the better on this topic, and particularly in the context of treating non-cancer pain. The results are good news, and completely consistent with other evidence. Ars Technica:

    Almost every news story one reads about the use of cannabis as a medical therapy contains some variation of disclaimer saying ‘more research is needed’ into the longterm safety of medical cannabis use. Now a tiny bit of that ‘more research’ has been published in the Journal of Pain. The headline result was that there was NO INCREASE IN THE NUMBER OF SERIOUS ADVERSE EVENTS in a group that used cannabis for chronic pain when compared to a group that did not.

    It’s hard to overstate how significant that kind of safety level is for any medication that helps with pain. Even the mildest over-the-counter analgesics come with serious risks (see How risky are NSAIDS?). Cannabis is not risk free — this study did find evidence of non-serious adverse events — but the total absence of serious adverse events is a big deal.

    (By the way, this science comes from Canada, which is where I come from. You’re welcome.)

26. Monte AA, Shelton SK, Mills E, et al. Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study. Ann Intern Med. 2019 04;170(8):531–537. PubMed 30909297 ❐ PainSci Bibliography 51836 ❐ Interestingly, digestive symptoms were more common with vaped cannabis than edible, while ingested pot caused more psychiatric and cardiovascular symptoms. Weird.
27. Takakuwa KM, Schears RM. The emergency department care of the cannabis and synthetic cannabinoid patient: a narrative review. Int J Emerg Med. 2021 Feb;14(1):10. PubMed 33568074 ❐ PainSci Bibliography 51837 ❐

    As cannabis becomes more widely available with the adoption of state medical cannabis laws, ED-related cannabis visits will likely rise. While cannabis has historically been considered a relatively safe drug, increased legal and illegal access to newer formulations of higher potency products and consumption methods have altered the management and approach to ED patient care and forced physicians to become more vigilant about recognizing and treating some new cannabis-related life-threatening conditions.

28. Pergolizzi Jr. JV, LeQuang JA, Bisney JF. Cannabinoid Hyperemesis. Medical Cannabis and Cannabinoids. 2018;1(2):73––95. PainSci Bibliography 51789 ❐
29. Not necessarily, of course. While many pathologies follow this pattern (spectrum conditions), not all do: some pathologies are subject to threshold effects, where the trouble only starts past a certain point, and are relatively consistent in their severity. We have no idea which type of pathology CHS is. IT could easily go either way.

30. A “prodromal” period is a period of early symptoms of a disease, usually preceding diagnosis. Many common diseases that ultimately have severe and obvious symptoms have surprisingly long and subtle prodromal phases, a phenomenon that has often been unrecognized or denied, but the term has become more common as the ubiquity of the phenomenon is increasingly recognized.

    Many scientific papers mention a prodromal phase for CHS, but often only in passing, and largely only as a relatively brief period of rapidly escalating acute symptoms before the first serious episode — which no doubt happens. But much subtler prodromal phHowever, after extensive perusal of posts on the large Facebook support group for CHS, I have encountered many anecdotal reports of much more extended and cryptic prodromal phases (e.g. “I had a lot of episodes of nausea and loss of appetite for months/years before my first vomiting episode.”)

31. Bahji A, Stephenson C, Tyo R, Hawken ER, Seitz DP. Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Apr;3(4):e202370. PubMed 32271390 ❐ PainSci Bibliography 52558 ❐
32. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research 2017, op. cit.
33. One of them stabbed himself repeatedly in the neck with a pair of scissors — one of the grisliest deaths I have ever heard of, and it happened to someone I’d had brunch with. He was a good man, and then his brain broke.
34. Parakh P, Basu D. Cannabis and psychosis: have we found the missing links? Asian J Psychiatr. 2013 Aug;6(4):281–7. PubMed 23810133 ❐
35. The famous rule — “correlation does not imply causation” — is an important idea, but also a misleading oversimplification. At the very least it’s missing a word, and it should be “correlation does not necessarily imply causation.” Or you could just rephrase it entirely. Edward Tufte, an American statistician who made the same point quite a while ago, suggested that a good informal re-wording would be, “Correlation is not causation but it sure is a hint.” Because correlation actually does “imply” causation, and many (if not most) events that occur in sequence that appear to be causally related are in fact causally related. Their correlation is not a coincidence. Clapping makes noise, braking stops cars, hot coals burn fingers.