Cannabis Can Paradoxically Worsen Pain


Written by:

Many people think of cannabis as a way to alleviate pain. After my friend was in a bike accident, she took cannabis edibles to escape the chronic pain that had developed in her back. Instead, she found that it made the pain unbearable. I dig into the cannabinoid research to find out why.

A case study in cannabis overdose worsening pain

A few months ago, I was getting ready to go out when I got a call from a friend. She sounded very spacey, as if she were high. She told me that she was calling from an ambulance. She had been hit by a car while riding her bike.

I rushed to the emergency room to meet her and after waiting for what felt like forever, I was allowed to go to her bedside. The doctor was just finishing up and said that she had a concussion, but that nothing was broken. She was released and I drove her home.

She remembered nothing of the accident. The police report suggested that she was hit by the car on her left side and was thrown onto the roof. She was left with significant pain, vertigo, and nausea.


“It would feel like I was being stabbed between my left scapula and spine. The pain radiated up and down from that spot. I also had a more constant dull pain in my lower back and right neck.


Unfortunately, she could find little relief from the pain.


“I was taking ibuprofen and tylenol around the clock. I tried therapeutic massage, acupuncture and a chiropractor. I didn’t want to take Vicodin because it makes me dizzy and I was already super nauseous and dizzy from the concussion. The pain lasted for months.”


Finally, at the recommendation of her friends (and even her acupuncturist!) she tried marijuana edibles. Her friends brought her cannabis extract-infused gummy bears. She started cautiously with a low dose and worked up to 5 gummies per day, a total dose of 50 mg THC.

However, she felt little effect from the gummies and decided to to switch products. This led to one of the most terrible experiences of her life.  Her friend brought her a cannabis chocolate bar, from which she ingested one square of chocolate, a dose which contained 45 mg of THC.


“I thought I was taking less of a dose than the gummies. I wanted it to have some effect since I was feeling so dysfunctional. After an hour, I started feeling the effects, but then the shift to being not fun was very quick. I lay down and basically it felt like each of my vertebrae were grinding on each other as waves of searing pain shot up and down my spine. It was really excruciating. I felt like I was going to die.”


Paradoxically, the pain had worsened with her ingestion of cannabis. This is how she described the pain on a scale of 1 to 10 before and after ingesting the cannabis-laced chocolate:


“My pain was at a 7 or 8. After, the pain was some of the worst I have felt. It was a 10.”


My friend had obviously overdosed. This is an important lesson that different cannabis edibles can not only have varying potency, but may also be absorbed differently – this will be the topic of a future post.

But how can we explain this experience? Cannabis is used by many to treat pain, so how can it be that it can also increase pain? At first it seemed a bit incredible, so I did a quick Google search. Sure enough, there are message boards where people have reported similar effects.

Before I get into the scientific evidence for marijuana increasing pain, I need to explain some background information.


A primer on pain

Pain typically starts with either potential or actual tissue damage. There are specific neurons called C-fibers that sense this damage and send a signal from the damaged tissue to the spinal cord.

pain signaling interneurons 3


Within the spinal cord, the C-fibers connect with second-order neurons that relay the signal up the spinal cord to the brain. Where C-fibers and second-order neurons intersect are interneurons that can modulate this signal. Specifically, inhibitory interneurons can decrease the strength of the signal sent to the brain. The brain then interprets the signal and produces the negative emotional state we know as pain.

After an initial pain signal is sent, sensitization starts to occur. This makes the site of tissue damage even more sensitive to pain. Even the undamaged area around the tissue damage becomes more sensitive. This is called hyperalgesia. Think of someone slapping you where you have a sunburn. Maybe it would have hurt a little anyways, but with the sunburn it is majorly painful.



The look of an individual who is experiencing the sensitization process of hyperalgesia.

Often, ongoing sensitization processes can cause more problems than the initial pain itself. Acute pain can turn into long-lasting chronic pain. Pain signaling is a dynamic process which can be modulated at the level of the periphery, the spinal cord, and the brain.  There are many different chemical mediators involved and cannabinoids are just one class. To get an idea, see below for an overview. It literally hurts my brain.


Pain hypersensitivity

Cannabinoids are in here somewhere, but I’m not going to try to find them.

Why the effects of cannabis on pain are difficult unravel

Pain signaling is already complicated, but cannabinoid pharmacology is complex in every way possible. Cannabis contains dozens of cannabinoids, which are a mix of agonists and partial agonists at cannabinoid receptors. The ratio of these is different depending on the cannabis strain and also the route of cannabis dosing. Furthermore, there are active metabolites, levels of which also change depending on dosing route. On top of that, cannabinoids have effects which are not mediated by either the cannabinoid CB1 or CB2 receptors.

It is likely that cannabinoids affect pain processing at all levels (peripheral, spinal, and brain), but through different mechanisms. For example:

  • Peripheral: Activation of CB2 receptors on immune cells reduces release of proinflammatory molecules 
  • Spinal: Binding to glycine receptors in the spinal cord potentiates the pain-blocking effects of glycine
  • Brain: Activation of CB1 receptors in the brain modulates emotional processing of pain signals


Evidence for cannabis exacerbating pain

Without a doubt, the complexity of pain signaling and cannabinoids make it a difficult topic to study. However, there has been progress in understanding these mechanisms and how marijuana may increase pain. I am going to highlight two key studies:

Study #1: The relationship between dose and pain relief is an “inverted U”

There are pain studies that can be done directly in healthy humans instead of patients who already have existing pain. These are called Human Experimental Models of Pain. The abbreviation for this is HEMP. I swear I’m not making this shit up.

The HEMP used in the first study is the intradermal capsaicin model. You know when you bite into a chili pepper and your mouth is on fire? That’s because of a molecule in the chili called capsaicin. Imagine purifying this molecule and injected it directly into your skin. That’s the intradermal capsaicin model.


capsaicin test skin


Capsaicin causes an acute pain at the injection site, but also activates the sensitization mechanisms to cause hyperalgesia in surrounding skin areas. This makes it a good model to study the pain associated with these processes.

The first study used the capsaicin model to look at analgesia from marijuana cigarettes. Subjects received marijuana cigarettes with 0% (placebo), 2% , 4%, or 8% THC. Capsaicin was injected into the forearm skin 45 min after smoking the marijuana cigarettes and subject’s pain was assessed. Here are the results:

  • The low THC dose did not affect pain scores. The THC dose was probably too low to be active.
  • The medium THC dose lowered pain scores, demonstrating the analgesic effects of cannabis.
  • The high THC dose  significantly increased pain scores. What the fuck!?


Capsaicin THC pain


These scientists were smart to administer different THC dose levels. To fully characterize the effect of a drug, you need to administer it over a range of doses. Typically, you expect that the higher the dose, the greater the response, until at some point the response reaches a plateau. This is called the “Emax” dose-response.

However, there are rare cases where as the dose goes up, the response goes up, reaches a peak, then comes down. In some cases there is even an opposite response at high enough doses. This is called the “inverted U” dose-response. It appears that cannabis fits the inverted U dose-response pattern for some types of pain.


Dose-response models pain

Examples of dose-response relationships. An ideal pain drug would look like the Emax pattern on the left. Cannabis dose-response for pain relief looks like the pattern on the right (but only for some types of pain).


This study confirms that cannabis can both decrease and increase pain at different doses, but how is this possible? This study  does not help us understand the mechanism through which this happens. Luckily, a subsequent study shed light on this mystery.

Study #2: Cannabinoids increase pain signaling in the spinal cord

I explained above how interneurons in the spinal cord regulate pain signaling of the main pain-transmitting neurons. Without the inhibitory interneurons being active, pain signaling can get out of control and even minor stimulation can be painful. These inhibitory interneurons are important for the development of hyperalgesia.

The second study, performed in mice, showed that inhibitory interneurons express the cannabinoid CB1 receptor. When the CB1 receptor is activated, the interneurons stop releasing the inhibitory neurotransmitters GABA and glycine. Without these inhibitory signals present in the spinal cord, pain signaling to the brain intensifies.


Interneuron with THC cannabinoid pain


Boom. A clear mechanism showing how it is possible that cannabinoids can increase pain. But following this logic, it would mean that blocking the CB1 receptor will decrease the same types of pain. These scientists also conducted a clinical study to see if this would happen.

They used rimonabant, which is a CB1 receptor antagonist (an antagonist is a molecule that blocks activation of a receptor.) At one point, it was developed as an obesity drug, but was pulled from the market due to serious side effects.



Side effects include anxiety, depression and suicidality. Bad things happen when you block your cannabinoid receptors!

Subjects were given either rimonobant or placebo prior to an intradermal electric shock. Although the acute pain from the shock was not changed, the hyperalgesia following the shock was significantly reduced.

These results confirm that a similar process occurs in humans as in in mice. Cannabinoids control the interneurons that regulate pain. Activating the CB1 receptor produces greater hyperalgesia and blocking the CB1 receptor reduces hyperalgesia.


Conclusions on cannabis exacerbating pain

The worsening of pain by cannabis is a real phenomenon. It was reported by multiple people and has been replicated in a laboratory setting.

One mechanism has been established and it occurs at the level of the spinal cord, where CB1 receptor activation decreases the effect of inhibitory interneurons on keeping pain in check. That’s not to say that there aren’t other possible mechanisms. For example, pain is modulated by your emotional state and the general dysphoria from a cannabis overdose may also increase pain levels.

It is important to realize that there are many different types of pain and cannabis can only exacerbate pain for certain types (otherwise this effect would be much more widely reported). CB1 receptor activation did not increase pain in animal models of inflammatory or neuropathic pain, which are some of the most common types of chronic pain. It is also dependent on the cannabis dose. Although there may be a dose level that causes pain relief, even a slightly higher dose may reverse the effect and worsen the pain.

If you are someone who has worsening pain with cannabis, it’s possible that blocking the CB1 receptor may help improve your pain. However, there are no CB1 receptor blockers that are currently commercially available. It may also be useful to carefully titrate your dose with a strain that is low in THC and high in CBD.  

In a future article, I will describe a cannabinoid that maximizes pain-relief without exacerbating pain.


Last modified: April 23, 2017

24 Responses to " Cannabis Can Paradoxically Worsen Pain "

  1. westwardbound says:

    “CB1 receptor activation did not increase pain in animal models of inflammatory or neuropathic pain”

    Are you able to elaborate on which type(s) of pain it was shown to increase in this study?

    • Prof of Pot says:

      I’m not sure if you read the sentence wrong…CB1 receptor activation did NOT increase pain in these animal models. This wasn’t from a specific study, but just my general sense from reading many studies of animal models that an increase in pain is almost never reported.

      • westwardbound says:

        I was reading it as that cannabis did not exacerbate inflammatory or neuropathic pain in these models, and assumed you meant it did increase other types of pain since you preceded it by saying there are many other types of pain and it only exacerbates some of these types. Maybe I am misinterpreted, regardless, this write-up has been very helpful and I appreciate the response.

        • Prof of Pot says:

          Sorry, I guess I misunderstood what you were asking. Outside of the studies described in this article, I have not seen any other studies showing that it increases pain. This was written over a year ago, so there could be new studies that I haven’t seen yet.

        • Maureen Krueger says:

          My doctor had me try medical marijuana uses primarily the CB1, but there is always a small amount of THC. The studies referred to is this article stated that small amount of thc, not much change in pain, medium amount of THC helped reduce pain and high THC actually made the pain worse. One of the studies stated there are different kinds of pain and that pain from central nervous system disorders were more likely to cause increased pain, while other types of pain like neuropathy, localized pain from injury or spine damage, cancer etc the results were mostly positive for decreasing pain.

          I took CB1 with low thc, but i was experiencing increased pain and after one week I woke in the night with burning pain all over my body, like a bad sunburn aND fatigue from the pain. I was becoming very emotional which was unusual. I stopped taking the CB1 and over the next week the pain slowl diminished and my emotions returned to normal. My body is hyper sensitive to everything. My guess is that even a small amount of THC caused my central nervous system to overreact. Obviously I don’t know for sure why my body reacted like that. I was really hoping the CB1 could get me off of the opiod pain medication that I have to currently rely on to control my pain.

          My dentist was amazed at how differently my nervous system reacted to the lidocaine that numbs the nerves than his other patients. Often times it would numb the nerves in different locations from where he expected. He always had to give me two or three times as many injections than other patients. Once he gave me the maximum amount of lidocaine and I could still feel too much pain, so I had to come back another day to finish the work.

          I give the dental example because it demonstrates that my nerves react differently from people who don’t have central nervous system disorders.

          I’m very disappointed it didn’t work and thought you would be interested as others may experience what I did. More testing is necessary to fully understand how the central nervous system affects the bodies ability to process medical marijuana and whether it affective or not for certain types of pain disorders as indicated in one of the tests you referenced in this article. I looked online and found very little on studies of medical marijuana and adverse affects.

  2. Raychelle says:

    Would the same reaction pertain to CBD oil from hemp? I take the non THC Hemp cbd and it helps tremendously. There is a lag time. But the next day, it’s working better than the first day. It’s weird. But it is unquestionable and way better.

    • Prof of Pot says:

      I haven’t heard of any reaction like this to CBD. It seems specific to THC and activation of CB1 receptors.

      • Vivi says:

        I have been on opiates for 3 years and have auto immune flare ups and fibro that causes pain. I was in a car accident 3 years ago that caused damage and increased pain. I have osteo in my knees, back, neck.
        Did not want to increase pain meds for increasing pain so tried CBD oil. Less than 1% THC and 20 mg CDB per ml. Started with dose of .3 ml and had worsening pain in knees, back and neck. But now have pain in shoulders, hands, elbows, etc. I was not expecting this. I thought CBD oil would help with pain and inflammation. Do not want THC high because I become anxious and paranoid.
        Tried dose again a few days later with same results.
        I continued with opiates and even that doesn’t get rid of CBD induced pain.
        Confused and disappointed. I held out so much hope that this would work.

  3. Candy Cane says:

    I’m super sad because about a year ago I would smoke and only have issues clenching my jaw here or there.. no body or nerve pain. Now when I smoke my neck hurts so bad I want to slam my head on my pillow repeatedly to make it stop and also my lower back hurts…this is from smoking random regular strains..I also tried smoking a vape pen and had the same issue. I found out I have degenerative disc issues and osteoarthritis from my neck down…I also have non alcoholic fatty liver so I can’t I basically feel hopeless when it comes to finding a recreational strain if mj to relieve my pain and let me chill. Also when I’m not high I don’t feel the nerve pain at all it starts after I’ve had one hit off my pipe and lasts two excruciating hours.

  4. Matt says:

    Thank you so much for this. I have some degeneration in my lower spine and for YEARS dealt with increasing pain that was immune to OTC pain relievers while thinking medical marijuana was helping. It was to the point that pain and restless leg-like symptoms where spreading to my upper back and down my arms. I was thinking I had fibro or something else going on but the doctors were stumped.

    I quit medical marijuana 3 days ago and my back pain is down over 90% and I am feeling great with renewed energy and mood. This was a life changer.

  5. Laura Gosselin says:

    I’m new to Medical Marijuana. I tried Indica Syringe. Afterwards, I feel my Tendons, Muscles, Bones weaken & ache all over in intensifying pain. I also feel my chest/lungs feel heavier with achy pressure. My body is twitching and easily startle jumps at sounds not typically annoying. I’m less active not only due to the increased pain but wiped out, dead tiresome. What should I do? I want this to work!

    • Hi Laura,

      Sorry to hear about your condition. Unfortunately I can’t give specific advice in terms of what products to use. It may be a process of trial and error. I recommend keeping a log of what you have tried – find out the cannabinoid ratio of whatever you use (hopefully they are all lab tested) then start from a low dose and work your way up, writing down the effects each dose had. If no doses are tolerated and provide relief, then switch to a product with a different cannabinoid ratio. Keep in mind that whatever route you take – edibles, smoking, vaporizing, can drastically change the ratio of cannabinoids that actually reach your body. If there are any medical dispensaries or practitioners specializing in cannabis near you, they may be able to provide more specific product recommendations. Best of luck!

  6. Ryan says:

    What fucking nonsense.. 2007 and 2009 study, absolute fucking nonsense.

    • Can you elaborate on what about it is nonsense?

      In a small subset of people, cannabis will make their pain worse. I don’t think that is arguable. Besides having seen it myself, there are many reports of it online (for example, see We don’t know the reason why it only happens in certain people – it could be the etiology of the pain, the person’s genetics, the strain of cannabis, the dose, or any combination of the above.

      Both the 2007 and 2009 studies were well designed and published in top journals. Although they don’t answer all the questions about this issue, they do provide some hints about the mechanism and contributing factors.

    • Maureen Krueger says:

      You obviously don’t suffer from chronic pain syndrome that has had adverse reaction to marijuana. Don’t judge that which you have no experience.

    • Jim K. says:

      Ryan, I have 8 bad disc, Bone spurs growing on my vertebrae and spinal arthritis. If I walk more than a few feet my pain shoots p for a few hours.
      I have been smoking pot since 1977 and never even thought of it for pain relief, just to get high. One time me and my brother tried to smoke an oz but after about 12 bowls, may 1/2 an oz. we stopped. Yeah quitters I know.
      Nowadays smoking mj makes my pain shoot up from a constant 6-7 to a 9-10. So I stopped smoking a week ago. I currently have 1/2 oz., edibles and hard candies. I will wait a few more days then try the candies again writing down not only before and after but any physical activity that can increase pain.
      Everyone’s pain, threshold to pain and reaction to drugs are different.
      When you get older (I hope with your statement you are still a teenager or your mind is very closed and I truly feel sorry for you, your loved ones and anyone that has to work with you) you will see what we all mean.

      Jim K.

  7. A. Kovacs says:

    Thanks so much for this post. I have chronic TMJ/neck pain and hoped to use MJ to decrease my dependence on opioids to manage my pain. Unfortunately, all the strains I tried (both indica and sativa dominant) tended to exacerbate my pain. Right now, my doctors are trying to determine if the pain is due to chronic tissue inflammation or nerve damage (getting an MRI next week). If the amplification of pain is due to the suppression of inhibitory neurons in the spinal cord, does this mean that pain originating from the spinal cord itself (e.g., cervical stenosis) is at higher risk of worsening with the use of MJ?

    • I don’t believe there is currently any evidence one way or the other indicating that pain originating in the spinal cord might be worsened by cannabis. Local inflammation in the spinal cord could certainly have an effect on cannabinoid processing of pain in theory, but it hasn’t been studied as far as I know. However, I have anecdotally heard of several people with spinal pain having their pain worsened by cannabis, so it is possible. Best of luck with reducing your dependence on opioids. It is unfortunate how few alternative treatment options are currently available and I really hope to see this change in the next few years.

      • Maureen Krueger says:

        I have chronic pain diagnosed as fibromyalgia in 2003 after a fall where I broke my ankle in 3 bones. The pain was excruciating. Cold, like ice packs made the pain worse. Looking back I have been hyper sensitive to pain my entire life. I suffer from debilitating migraines also. With the recent focus on opiod OD’S my doctor suggested trying marijuana capsules that were low in THC. After two weeks I noticed my pain increasing and I have become very emotional and feelings of depression and fear. I didn’t associate with the marijuana until last night when I woke up after 2 hours sleep and from high pain level, like my nerves are burning all over my body. At first I thought it was from colder weather the past couple of days, bUT as I thought about it my usual reaction to weather changes is aching muscles, not burning nerves. Then I thought about any changes in diet or medication and realized the only change is the marijuana. This was very surprising because I had always heard it reduces pain. So I started looking on the internet and came across your article. The difference I see is that my doctor said this is low in THC. I talked to her today and she advised me to stop taking it, which I already decided to stop and give my body about a week to detox. My body is hyper senotice to light, sound, touch (if sitting close to some one and our arms are touching my arm will start to ache. Necklaces, bracelets, watches and rings cause pain. I have tried many kinds of therapy including feldenchris, massage, bowen, skener, and opiods. One opiod helps the most which is nuycenta but the maximum is 2 per day. At night I take morphine pill. With the new focus on opiods it is becoming very difficult to get prescriptions filled and recently had to wait 16 days for my prescription relying on morphine to get me through and that makes me groggy. I was hoping marijuana might be the answer as long as THC was low. I’m very disappointed and not sure where to turn next. For now I have to rely on my pain medications. I’m under very controlled doctor care and have been successful in having good days to balance out the bad ones. Thanks for your article and the info on the studies tgat have been done. I think more studies need to be done and some exemptions from some of the new laws for those who truly suffer from chronic pain that at this time has no cure.

  8. Tim says:

    Another thing to consider is the type of high you get from certain strains.

    I dislocated my shoulder, and found that smoking sativa strains tend to bring on the “twitches” much more than indica. My pain increased DRASTICALLY, since literally every muscle in my body would randomly twitch over a period of 30 minutes to 1 hour after smoking. No matter how hard I try to relax my muscles, they stay tensed up, and twitch, which is MURDER on an already injured shoulder.

  9. H.C. Desilay says:

    I have CRPS, formerly known as RSD. For me, the pain is almost always exacerbated by smoking cannabis. I also have MS (history predates my Dx with CRPS by 20+ years). I never experienced increased pain when I smoked mj to calm the light neuropathic pains I had with M.S. My daughter is an RN and lives in Denver. When I last visited her, she tried a cannabis cream on my CRPS-affected foot. The pain intensified and lasted longer than when I smoked canabis.
    I have a RX for marinol for nausea/loss of appetite. Since developing CRPS, I was shocked, amazed, to discover that one marinol exacerbated the nerve pain in my CRPS foot! It also makes me feel -slightly- high, not a pleasant buzz. It does work for naseau tho, as cannabis does.
    The only cannabis I can smoke without intensifying my pain is high THC “wax.” One draw on a pipe and I can enjoy the calming, social benefits I used to enjoy from smoking any strain of cannabis. I enjoy the feeling of relaxation cannabis with THC gives. I’ve tried vaping a high quality organic CDB oil and experienced zero pain relief. Same with CDB oil. Zero nerve pain relief.
    I look forward to the day medical mj is legal in my state so I can find/be prescribed the type of strain the THC wax is.
    I respectfully disagree that the main reason mj can exacerbate pain is due to overdosing. Just 1 single toke of satvia or indica or 1 small dot of mmj ointment, exacerbated my nerve pain. I’ve tried over 20 times/strains with the same results. But 1 toke of high-concentrate THC oil/or “wax” and I don’t experience increased pain that even 1 marinol capsule causes.
    Of note, the only thing that has brought my CRPS pain down to a “1” is compounded Dextromethorphan. Sadly, it also increased my core body heat, which exacerbated my MS symptoms of malaise, extreme fatigue and weakness. Clearly, in my case, an NMDA- receptor antagonist (?) works to lessen nerve pain. My pain dr prescribed 100 mgs every 12 hours. I did not feel high or drugged, only happy to be free of pain. But the sedating effects made is impossible to get out of bed. The other med people are finding successful for treating CRPS (under a doctor’s close administering and dosing) is IV ketamine. Might there be any canabis strains that work on the NMDA receptors?
    Your thoughts would be appreciated!

    • Sorry to hear about your struggle with CRPS and MS. It does not surprise me that a cream would cause a longer-lasting pain than smoking. Local levels of cannabinoids in the skin stay high for much longer with a cream (due to slow absorption through the skin) than after smoking. However this also shows that the mechanism of your worsening pain is probably at local level (in your skin) rather than through the spinal interneurons as I described above. As far as I know, a local mechanism of cannabis increasing pain has not yet been discovered, but there is not much research in this specific area.

      It is interesting that many different strains of cannabis worsened your pain, but wax does not. It goes to show that a large part of medicine is experimenting until you find something that works. I am not sure why wax works best for you. I would think that it is due to the specific ratio of cannabinoids (and maybe the high THC percentage) that helped. Although Marinol, which is pure THC, did increase your pain, so it cannot be the high THC alone.

      I did not mean to imply that a high dose is the culprit in all cases of increased pain. This may be true for some people and not for others. It was true for my friend in the bike accident – it was only when she took a very high dose that pain increased.

      I am not aware of any cannabinoids that work directly on NMDA receptors, although I will keep an eye out. There is a lot of “cross-talk” between the cannabinoid system and glutamate/NMDA system, so cannabis may indirectly have an effect on NMDA receptors. I have seen a lot of promising research recently on IV ketamine, so I hope that will provide patients with another therapeutic option.

Leave a Reply

Your email address will not be published. Required fields are marked *