New Research on CBD and Opioid or Heroin Addiction, Withdrawal, Tolerance, and Recovery
June 09, 2020
We've covered CBD and addiction generally already but the most exciting news is on the opioid front.
Not a minute too soon.
We'll leave the stats to other sites as we want to focus on research speaking to recovery.
Two big studies have come out on CBD and opioid withdrawals and recovery directly .
We'll also look at mechanisms behind how it addresses tolerance and recovery of the natural opioid system which is key.
We'll also touch on pain since that is likely what brought us to opioids to begin with (on the prescription side anyway).
Our main focus will be on addiction. How opioids hijack our reward system and what CBD does within that pathway.
We'll cover these areas:
- A quick introduction to your opioid system
- The opioid system and pain
- The opioid system and addiction
- Opioid tolerance - the key to withdrawals
- Opioids and dopamine - "do that again"
- The endocannabinoid system and opioid addiction
- Research on CBD and opioid addiction
- How long does CBD take to work
- How much CBD to take for opioid recovery
- What's the best CBD for opioid addiction
Let's get started.
A quick introduction to your opioid system
We really need a quick intro.
After all, this is the system in your body that opioids directly interact.
Once you see its role in the body, it may shed light on why opioids spoke to a person in the first place.
After all, some people can take pain meds and walk away while others are almost instantly mired in a sea of misery.
Why?
First, let's look at three key actions of our opioid system:
- To create pleasure or euphoria
- To offset pain
- To support the stress response
Let's really break these down because they're key to why people keep using (or fall back in).
Many people think that dopamine is the pleasure agent in the reward circuit but it leans on the naturally occurring opioids in our brain and body for that side-trick.
Euphoria or pleasure comes from our opioid system. Why?
It's the main way that the brain/body rewards us for activities that should promote our survival.
Food, water, sex….even social interaction!
In fact, when they isolated rats, researchers saw direct effects in the opioid system.
And the opposite is true:
Social interaction increased opioid binding in the parafascicular area of non-isolated rats.
https://pubmed.ncbi.nlm.nih.gov/7549454/
We've covered the effects of social rejection on serotonin (see tryptophan as social stress support) already which is fascinating.
To see our pleasure/pain pathway guide changed as a result is equally powerful.
Addictive drugs are addictive for a reason. Two actually.
- They boost dopamine (we'll discuss later)
- They boost the opioid system (cause pleasure or hedonic technically)
Broccoli only gently nudges these two which is unfortunate!
The study we did on CBD and dopamine looked at how meth can send dopamine through the room.
Almost guaranteeing addiction.
Essentially, opioids have hijacked this reward system and focused it like a laser (via dopamine) on getting more of the drug.
The initial introduction may have been due to pain.
Before we jump into pain, let's look at one more intriguing aspect for both why opioids may speak to certain people so loudly.
Opioids and stress response.
Most people don't know about this one but it's critical for recovery.
The leading trigger for people to relapse is...stress.
It turns out that our natural opioid system is part of the counterbalance to our stress systems (HPA, cortisol, etc) along with the endocannabinoid system (we'll touch on later).
As researchers put it:
The most consistent finding among such studies using different species and stressors is that opioids not only diminish stress-induced neuroendocrine and autonomic responses, but also stimulate these effector systems in the non-stressed state.
https://pubmed.ncbi.nlm.nih.gov/11383975/
This is fascinating.
We've looked at the power of stress to elicit a slew of mental health issues:
- CBD and neuroinflammation
- CBD and depression
- CBD and anxiety
- CBD and cortisol
- CBD and inflammation
- CBD and schizophrenia
You get the picture...almost every mental health issue is tied to stress response and/or inflammation.
If a person's system is under stress, opioids may initially (before the addiction kicks in) speak to this deficit directly.
We can look to genetics for this clue.
There are targets that appear which reflect the risk for addiction to opioids.
Three are prominent and fascinating:
- OPRD1 - gene that regulates, builds opioid receptors
- ESR1 - gene for estrogen
- COMT - gene for removal of neurotransmitters
Read back over that!
The OPRD1 makes sense...it's directly involved in making opioid receptors.
If a person naturally doesn't make enough opioid receptors, taking any opioid externally essentially becomes self-medication.
In our addiction review, we looked at how most addictive drugs start by filling a natural gap:
- Benzos - GABA, our "brake pedal"
- SSRI's - serotonin, our "feel good" neurotransmitter (although much broader than that)
- Alcohol - GABA and serotonin (goodness...no wonder it's the biggest addiction)
- Cannabis - anandamide (we'll touch on this below in the endocannabinoid system)
- Stimulants - glutamate, our "gas pedal"
And of course...opioids….our naturally occurring opioids called endorphins.
Back to our stress response system, researchers found a curious connection between the OPRD1 gene and our main stress hormone:
Our results confirm the role of minor G allele as a risk marker of opioid addiction in the Pakistani population through its role in elevating the stress responses (cortisol).
https://www.endocrine-abstracts.org/ea/0056/ea0056p669
Essentially, these people naturally felt too much stress as a result of lowered opioid receptor gene activity.
Self-medicating.
In our tryptophan review, we saw how early social rejection primes the nervous system for elevated anxiety and stress response.
Check out CBD and serotonin to understand why.
The other two genes are very interesting.
ESR1 is a gene for estrogen function. Women are much more likely to not only experience chronic pain but suffer from opioid addiction.
Check out CBD and estrogen or estrogen review for perimenopause to understand how estrogen molds pain response and boosts serotonin.
The final gene there is COMT. Another key player in stress response.
Goodness...look at what it does:
COMT is also associated with greater levels of cortisol and HPA axis dysfunction (which is largely responsible for the body's ability to calm itself and de-stress)
Remember, part of the opioid's system complex and interweaving role in the body is to offset stress response (such as cortisol or HPA axis activity).
Look at what happens for roughly 20% of the population:
COMT gene variation which limits the body's ability to remove catechols (a specific type of molecule that includes dopamine, norepinephrine, estrogen, etc.) by 3-4 times.
3-4 times. Adrenaline is in that family and cortisol is attached.
Now imagine if a person has 1 or more gene variants where they either don't process endorphins correctly (OPDR1) to offset stress or don't break down the stress chemicals (COMT).
That is a risk bonanza potentially for opioid addiction.
Remember...opioids have a side-gig of offsetting stress in the body.
And then they break a leg or something.
The opioid system and pain
This is how most people think of the opioid system due to its role in medicine.
Our opioid system is the first responder for pain.
Yes, it's guided by serotonin and other systems but the heavy lifting is done by the opioid responders (called endorphins).
There are three opioid receptors in the body and one of them really drives pain response:
The lack of mu-receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence.
https://www.sciencedaily.com/releases/2007/10/071014163647.htm
Analgesic just means pain relieving.
Get rid of the mu-opioid receptor and pain relief goes away from morphine.
Keep in mind that inflammatory pain is a different pathway and not really addressed at the root cause of opioids.
Check out CBD and inflammation here.
Opioids simply address the sensation of pain itself.
There's a complicated array of processes that go into pain with the immune system and inflammatory agents at play.
The opioid system is just the signal to the brain...to us...that's something is wrong.
There's some pretty interesting research now on chronic pain and how pain gets "stuck" at the localized nerves (say the feet) or in the nervous system itself.
Glutamate, our nervous system's "gas pedal" looks to be a key pathway going forward.
The research on topical ketamine for complex regional pain (as it's called) is fascinating.
Essentially, it calms glutamate activity at the peripheral nerve.
Glutamate is needed for the whole nervous system to work but it's toxic at higher levels to nerves.
Check out the review on glutamate to understand better why this is such a powerful pathway that's slowly gaining speed. The review of NAC is equally interesting.
Here's the problem with long term opioid use in terms of pain.
The body eventually builds tolerance.
It will start to actually reduce the number of opioid receptors to offset the outside boost to this system.
Eventually, you'll need the opioids just to NOT feel intense pain.
Read the CBD and tolerance review to unravel this process and we'll touch on it later.
It figures into addiction as well...let's got here now.
The opioid system and addiction
We need two effects for true addiction:
- A boost to dopamine - "do that again" key to learning both good and bad
- Tolerance - a reaction from the body in the opposite direction of the opioid
Surprise...we have both with opioids.
Let's look at the first piece...effect on dopamine
Opioids and dopamine - "do that again"
Interestingly, opioids act as a wet blanket on brain activity.
They suppress a number of neurotransmitters across the brain.
This figures into its anti-stress response you see similar to anandamide (part of the endocannabinoid system) or THC, it's a substitute.
So...how is it boosting dopamine if opioids naturally suppress activity?
Researchers found out it does this by suppressing the "brake pedal" GABA activity in dopamine neurons!
Stay with us...essentially, it takes the brake off dopamine neurons!
It is concluded that hyperpolarization of the interneurons by opioids reduces the spontaneous GABAmediated synaptic input to the dopamine cells. I do, this would lead to excitation of the dopamine cells
It does this with gusto (i.e. hyperpolarization).
The research gets even more interesting and shows just how complicated our bodies are.
Why are opioids so addictive?
It turns out that one of our natural opioids called preprodynorphin actually controls dopamine tone.
The tone is a word for our baseline dopamine. Think of tone as the ocean and spikes as the waves (from food, water, sex, or opioids).
This is really important as the tone is what is affected (reduced) by tolerance and it's key to both recovery and why we might have been drawn to opioids to begin with (low tone).
As researchers put it (we'll decipher):
This is especially important since we and others have shown that dynorphin peptides, which are the natural endogenous opioid ligands of the kappa-opioid receptors, serve to modulate dopaminergic tone and countermodulate cocaine-induced dopaminergic surges.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202505/
Our natural opioids have a side-gig of managing our dopamine reserve and balance.
In fact, improved tone would offset the surges caused by addictive drugs.
So...we're getting hit two ways...surges in dopamine and effects on the underlying dopamine tone.
Now...we have to look at tolerance if we're ever going to get out of this.
Opioid tolerance - the key to withdrawals
Simply put...the body doesn't like when outside forces mess with critical pathways such as our opioid system.
This is true for all the neurotransmitters as well including dopamine.
We've covered this in detail at our CBD for THC addiction or CBD for alcohol addiction.
This is why you need more and more opioids to get the same feeling and eventually, the opioid just taking you out of the pain it caused by downregulating your natural system.
Studies have shown that the brain will actually reduce the number of opioid receptors and even suppress sensitivity.
Remember...we're only talking about the sensation of pain....opioids have no effect on the cause (inflammatory processes or nerves stuck in pain mode).
As we've seen, opioids control many other aspects of how we feel (stress response, social reactions, dopamine tone, etc).
All of that goes down as well since the body is frantically trying to offset the unnatural surges of opioids.
Dopamine will also be suppressed and that's a whole other kind of bad.
Too little dopamine and you can't get out of bed or do much of anything.
Check out CBD and tolerance and we'll look at why neurogenesis is key to this process.
Let's finally turn to CBD and opioid addiction….what we've been waiting for.
Research on CBD and opioid addiction
Let's finally get into the research.
There are two big studies we'll start with specific to CBD and opioid addiction.
First, the craving side of it.
This is key to recovery.
Their findings:
Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues.
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191
This is fascinating since the craving comes from tolerance and dopamine imbalance.
We'll look at those specifically later.
The interesting piece was this:
CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure.
How could the effect last for 7 days following a short treatment?
They even found effects on heart rate (out of our control) and cortisol (reduced) levels.
Remember how cortisol is our key stress hormone and opioids offset its effect from stress?
In fact, people with poor stress responses may naturally be self-medicating with opioids.
Check out CBD and cortisol or CBD and stress for more information.
The craving is a function of learning (dopamine shapes our learning for survival) and tolerance (our natural levels are now so depleted).
Check out CBD and dopamine to learn how to make it our servant and not our master.
The other big study is brand new and very exciting.
Results: Over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens. Almost all CBD users (94%) reported quality of life improvements.
https://pubmed.ncbi.nlm.nih.gov/31711352/
They found a significant improvement in sleep which is a key issue with recovery.
This study was for people who became addicted to opioids due to pain which is critical.
Let's drill down into all the components we looked at above.
We'll look at these areas:
- CBD and opioid withdrawal symptoms
- CBD and opioid repair
- CBD and stress
- CBD and pain
Let's get started.
CBD and opioid withdrawal symptoms
The common list is here:
- muscle aches
- restlessness
- anxiety
- lacrimation (eyes tearing up)
- runny nose
- excessive sweating
- inability to sleep
- yawning very often
https://www.healthline.com/health/opiate-withdrawal#symptoms
Pain, anxiety, irritability (restlessness), and insomnia are the big ones.
This just happens to be the sweet spots for CBD's activity.
We've covered them in detail here:
Restlessness and irritability (as well as the others) point to imbalances in the serotonin and dopamine systems.
Serotonin shapes our pain sensitivity, sleep, stress response, and the restlessness associated with opioid withdrawal is very reminiscent of serotonin syndrome (see CBD and serotonin syndrome).
Remember how opioids are wet blankets on activity including neurotransmitters.
With long term use, the body tries to offset this effect which would mean upregulating serotonin pathways.
Once the wet blanket it taken off, there's excess serotonin in the syndrome.
Check out SSRIs and suicidal thoughts (extreme restlessness) to see the extent of this.
So the key is to normalize or rescue serotonin function as quickly as possible.
Serotonin also controls dopamine function so the two are interconnected (behavior and reward circuit).
This may be CBD's greatest gift.
A perfect study for this is when researchers created an injury on mice which led to pain, anxiety, and imbalance (exhausted) serotonin.
Look at the effects:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://pubmed.ncbi.nlm.nih.gov/30157131/
Allodynia is pain. 5-HT is serotonin.
"Normalized" serotonin. Check out CBD and serotonin to understand all the ramifications of this effect (anxiety, depression, sleep, pain, etc).
They went on to say:
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
So…
- Reduction in pain
- Reduction in anxiety
- "Rescue" serotonin function
We just listed off the bulk of opioid withdrawal symptoms!
Sweating and fever are also tied to serotonin imbalance (ask the ladies in perimenopause - estrogen directly boosts serotonin).
We also covered CBD's similar effect on dopamine at our CBD and dopamine review.
Dopamine is directly tied to the withdrawal effects of opioid withdrawal.
The studies on CBD and schizophrenia (symptoms tied to both too much and too little dopamine in certain brain areas) are powerful in terms of balancing complicated systems...
We'll discuss what research says on how much, how long, and in what steps for CBD in terms of the initial withdrawal.
CBD and opioid repair
We looked at rescuing serotonin function.
What about opioid function which will severely depressed as a result of long term use.
Remember, that's how tolerance works.
It goes all the way down to the genetic level with genes being turned off for making opioid receptors and intermediaries.
Let's introduce a term that's going to become very popular over the next decade.
Neurogenesis. It's the process of how the body repairs and grows new connections.
This is the key to reversing the effects of long term opioid use or any drug for that matter.
It's securely under the sway of serotonin (at least partially).
In fact, that's why SSRIs, the most common class of antidepressants, take weeks to work.
Research shows that their primary effect for depression and to a lesser extent, anxiety, is by increasing neurogenesis.
Check out our review on How SSRIs actually work.
The heavy lifter of this system is BDNF, our brain's fertilizer.
CBD's effect on serotonin may be its biggest trick in that it spurs neurogenesis and even BDNF!
Check out CBD and brain repair or CBD and BDNF for more info but a quick example.
Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908414/
We looked at CBD and cannabis addiction here.
The hippocampus is key to memory and emotional control.
It's also the most vulnerable area of our brain since it's designed to constantly change (due to memory).
Why is this important?
Chronic administration of morphine decreased neurogenesis by 42% in the adult rat hippocampal granule cell layer.
https://www.pnas.org/content/97/13/7579
Goodness...the very thing we need to get out from under opiates (brain remodeling) is suppressed by opioids.
This process is at the heart of unlearning old habits and learning new tricks.
It really lies at the intersection of every mental health issue we come across now in terms of healing and recovery.
This includes rescuing our opioid receptor system back to normal (maybe better than normal if we originally used opioids to self-medicate for a depressed system).
We've also covered this in our CBD and benzos for GABA receptors (same principle).
Remember how the opioid system functions as a stress response buffer?
CBD and stress
We have another system that is key to dealing with stress.
Our endocannabinoid system.
It's tasked with balancing other key systems in reaction to stress:
- Endocrine system - hormones including cortisol and other stress hormones
- Immune system - inflammatory agents which like at the heart of the cause of pain
- Nervous system - neurotransmitters like dopamine, serotonin, and opioids!
Studies have looked at the effect of chronic stress and trauma on natural opioid function.
Lots of studies...such as:
Chronic exposure to stress, such as the case with PTSD, taxes kappa opioid receptors, however, causing the receptors to retract inside cells, leaving dynorphin without a place to dock. As a result, patients can experience dysphoria, characterized by feelings of hopelessness, detachment and emotional unease.
https://www.sciencedaily.com/releases/2014/09/140917172738.htm
This is about the exhaustion of our natural opioid system from stress, trauma, and yes….pain.
See how it quickly manifests itself into psychological effects?
Again, our opioid system is very complicated and connected across a range of seemingly unrelated pathways.
Social rejection. Early infection. Stress. Trauma. All related.
What does this have to do with CBD?
CBD supports the endocannabinoid system which is our primary balancing agent against stress.
We're using the word stress as an overarching umbrella for anything that pushes on the system (infection, stress, trauma, etc).
You have a powerful stress response agent called anandamide.
It's named after the Hindu goddess of bliss, Anand so you get the picture.
CBD has been shown to directly support anandamide levels with a range of stress calming effects.
As an extreme of what can happen when our brain is under duress:
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
Check out CBD and stress for anxiety here.
The study on CBD and public speaking is a perfect example of its effects under high duress.
This study was carried out on people with a diagnosed social anxiety disorder who would speak publicly.
The effects were impressive - check out CBD and public speaking phobia.
Finally, the reason most people found opioids to begin with.
CBD and pain
We compared CBD and the pathway used by Tylenol and Celebrex here.
First, pain is under the control of serotonin (hence the monthly period pain when estrogen drops for women).
As we saw in the study above, CBD rescued serotonin and reduced pain sensitivity (allodynia).
As Mayo clinic put it:
There is a growing body of preclinical and clinical evidence to support the use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction.
https://pubmed.ncbi.nlm.nih.gov/31447137/
There's a massive NIH study of CBD for pain going on now.
Let's get to some practical questions.
How long does CBD take to work
There really are two phases.
- The withdrawal period
- The recovery period
The withdrawal period is obvious and very similar across a range of different drugs.
There's a difference between fast-acting opioids and slower ones in terms of when the symptoms generally startup.
The effects of CBD are very fast for anxiety, depression, and sleep.
Hold the CBD under the tongue for up to 60 seconds to speed and increase bioavailability.
This speaks to the initial withdrawal symptoms for roughly the first week following abstinence.
The longer-term effects are more interesting.
This is the neurogenesis piece which is key to rewiring the brain (which has been strongly wired towards opioids).
Studies on benzos and GABA receptors showed they normalized after 4 weeks.
We can assume the same process for the opioid receptors and our natural pathway.
Other studies pointed to 6-8 weeks for neurogenesis effects.
Based on this, we can estimate a higher dose for the first week (or until symptoms resolve) and a reduced dose through 2 months and even beyond for good measure.
For the long term recovery aspect, this is the same result from exercise, mindful meditation, and even CBT (cognitive behavior therapy). They just do this at a slower pace via petition and boosts to BDNF.
We looked at this in our CBD, exercise, and mindful meditation for neurogenesis review.
Finally, check out our review on NAC for mental health and addiction as well as psilocybin for addiction.
Very interesting stories happening right now. The NAC (N-acetyl cysteine) is a slam dunk due to safety, cost, and availability.
NAC and CBD combined could be powerful allies for opioid addiction and recovery.
What about dosages?
How much CBD to take for opioid recovery
Looking at the two phases above (withdrawal, recovery), it speaks to different dosages based on research.
First, the initial phase which is so debilitating.
The study above tested at 400mg and 800mg for the withdrawal symptoms.
Other studies point to 600-800mg dosages per day for severe issues (schizophrenia, bipolar, depression, etc).
For this reason, research is generally pointing to 600-800mg for the first week or until the initial symptoms calm down.
This can be broken up as needed. Perhaps with each meal or before bed (sleep is a major issue).
Safety has been tracked up to 1500 mg doses in a day with a strong profile.
Some studies on cancer symptoms were even at the 2-3 gram level.
Research is pointing to 600-800mg for the initial serious issues.
Once those settle, 300mg is showing in research as the peak for neurogenesis.
This is our goal after all for actually being successful!
Beyond the 300mg, neurogenesis actually goes down a bit so that's our goal for the long term 1-2 months following the initial withdrawal period.
Personally, we take 300 mg daily for years now since chronic stress doesn't really seem to subside right now.
There are studies on taking CBD long term or how long does it take for CBD to work here.
The net:
- First week - 600-800 mg daily
- Week 2-8 - 300 mg daily
Long term, the 300mg is key to a host of different pathways tied to brain plasticity (ability to change).
Finally, what type of CBD?
What's the best CBD for opioid addiction
First, some basic requirements:
- Organically grown in the US at an FDA registered farm
- 3rd party tested
- No THC (THC may adversely affect hippocampus neurogenesis)
- No pesticides
- No solvents
- No heavy metals
- No mold
- No bacteria
We actually test ours twice since our whole family takes it.
Then there's the question of CBD isolate versus full spectrum.
We focus on isolate for two simple reasons:
- All the research above and through the literature is based on CBD by itself - isolate
- Histamine issues with full spectrum
The latter may be the difference between CBD products helping you and other products making you feel pretty terrible.
Roughly 40-60% of the population has histamine or allergy issues.
All that plant material in full-spectrum can send these people the wrong way.
We're already dealing with opioid withdrawal symptoms without throwing on histamine reactions.
In fact, just look at the symptoms:
Opiates have long been known to cause the release of histamine from mast cells, resulting in several undesirable effects, such as hypotension, urticaria, pruritus, and tachycardia
https://pubmed.ncbi.nlm.nih.gov/7694026/
In layman's terms...raised blood pressure, hives, itching, and a racing heart.
Sound familiar?
We want CBD isolate to avoid compounding this issue.
Finally, there's affordability.
There's lots of junk products out there with 250 mg in a bottle for high prices.
They're just taking advantage of people.
The research clearly points to doses at 400 mg+ for opioid withdrawal and addiction.
We purposely price our 6000mg bottle at about 2 cents per mg and that's before discounts available up to 30%.
We do this because we've been there before with benzos and SSRIs (founders story is here) and it almost broke us.
With new research coming out now on CBD and opioid withdrawal or recovery, any effort to reduce the suffering is part of our goal at IndigoNaturals.
Hopefully, you now know the why's, how's, and when's to opioid addiction and more importantly...rescue.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.