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Our participants did not have chronic pain, but we measured the impact of cannabis combined with this very low oxycodone dose by eliciting a pain response using a standard pain test. We found significant analgesia, or a decrease in the pain response, when participants smoked the active cannabis in combination with this very low dose of oxycodone.
We did not see pain relief in this model with cannabis alone or that dose of oxycodone alone. An important aspect of the study is the question related to the possibility that if we observed this cannabis-opioid synergy for pain relief, would we also see an enhancement of some of the adverse effects?
One adverse effect that we measured was the impact of the cannabis-opioid combination on abuse liability. We found that the drug combination did not increase cannabis's abuse liability. For example, oxycodone did not increase cannabis self-administration, a gold-standard assessment for a drug's abuse potential.
Importantly, we did see small increases in abuse liability ratings for oxycodone when combined with cannabis. We did not look at opioid self-administration and that is an important next step. The study was designed to begin to understand the mechanisms that are driving some of these state level and epidemiological findings that were discussed earlier, as well as the pharmacological interactions to help elucidate can cannabis, or importantly, can cannabinoids in general be used as an adjunct or a substitute for opioids for pain relief.
In future studies, it would be very important to look at the dose-dependent nature of this effect since we only assessed one active cannabis strength. Another research priority is to assess the effects of cannabis that has a variety of other cannabinoids, especially cannabidiol, since there is evidence in the literature that cannabidiol in addition to THC can also help pain.
Determining if these findings generalize to a population that has chronic pain under controlled procedures will be fundamental to conclusions related to the clinical utility of cannabis and cannabinoids in combination with opioids to help treat pain.
To respond to the earlier comment regarding the difficulty of studying cannabis and opioid interactions under controlled procedures, there are ways that we can do this. We can look at other FDA approved cannabinoids in a patient population, such as nabilone or dronabinol, in combination with very low doses of opioids to see if we can increase the analgesic effects of opioids, while also mitigating their adverse effects.
What studies do you think are needed now to be able to come to a firm conclusion to this. If you had to have just one ideal study, what do you think would be the strongest one to perform? The strongest study would be a placebo-controlled study with a pain population assessing the impact of cannabis or cannabinoids and placebo in combination with low opioid doses.
Both the pain-relieving effects and a range of adverse effects would be measured, including abuse liability, cognitive effects, and, importantly, respiratory depressant effects. We do not think that cannabinoids and opioids will interact to enhance the risk of opioid-induced respiratory depression, but it is a critical end-point to address if we want to ensure the safety of opioid—cannabinoid combinations.
This type of study, utilizing a large pain-patient population, is critical in demonstrating the generalizability of our recently published study findings. And, I think this is feasible. It can be done. It is just a matter of optimizing the study design and figuring out which pharmacological tools to study with respect to both cannabinoid and opioids. For instance, cannabinoid opioid-sparing effects may differ based on the opioid's mu agonist affinity and efficacy.
An important question to ask is which opioid agonist would be optimal to administer with cannabis or a cannabinoid to ensure analgesic synergy while also mitigating adverse effects? Do we test a partial agonist like buprenorphine or do we assess the effects of a full agonist? With respect to your last point, actually, the Le Foll review pointed out that the synergism factor between codeine and cannabinoids and THC is much stronger, 9.
So far, we have looked at the cannabinoid—opioid interactions from medical and public health perspective, but we should not forget the societal context, in particular the legal context, which as we all know is extremely confusing.
Graham Boyd, as a lawyer who has been active in this field for some time, can you give our readers the lay of the land from the legal perspective, again on the interactions between the legal status of the two classes of drugs and how that interferes with research and how it can impact also public health?
Thank you for that question and lead-in. Within the whole range of opiates that we are concerned, all are prescribed by physicians and can be researched with relative ease, with the exception of heroin, which is in the Schedule I, the most restricted schedule.
And that, too, is where cannabis is placed, in Schedule I. Let me just give a bit of background about this. If a drug has any potential for abuse, it is put into one of the schedules and if it is a high level of abuse and of no medical value, according to the federal government, then it is put in that most restricted schedule of Schedule I. And, surprising to most people, the less restrictive Schedule II is where you find cocaine, methamphetamine, and many of the most powerful opiates because those substances do have recognized medical use, despite having a high potential for abuse.
At this point, the overwhelming majority of scientists, medical professionals, and ordinary people agree that cannabis being in Schedule I does not make a lot of sense, and yet efforts to reschedule cannabis have been blocked repeatedly.
DEA's own administrative law judge conducted a thorough review of evidence, ruled in favor of rescheduling, but was overruled summarily by the DEA Administrator.
After years of litigation, Congressional hearings, and thorough exploration of every conceivable path, DEA's roadblocks led to activists to decide to go directly to state voters to pass the medical marijuana laws through direct ballot measures. Interestingly, the federal government responded by saying marijuana can never be medicine. Donna Shalala, the Secretary of Department of Health and Human Services, was among the Cabinet officials who threatened to arrest any doctor who recommended marijuana to patients in California.
I was the lawyer who represented doctors, including Marcus Conant, who was one of the first doctors to diagnose AIDS in a lawsuit that established a First Amendment right to recommend marijuana to patients. This has created an incredibly messy situation in the sense that cannabis is legal under state law, yet illegal under federal law, and retention of cannabis in Schedule I has left it in the place where doing research, as the other speakers have noted, is incredibly hard to do.
This creates a Catch because the only way to move something out of Schedule I is based on research and medical evidence and yet the barriers to doing that very research are so strict. So, that is where we stand right now. In recent years, and I think really because of the proliferation of these state laws which make cannabis so much more accessible, and because of the anecdotal and some research evidence of medical efficacy, the federal government has to some extent loosen the restrictions on doing research.
But it still is, literally, among the hardest substances to do any kind of medical research. You have to get a DEA registration, have security.
You have to have a safe or a vault to keep the substance. The DEA visits you to make sure that it is secure enough. Eighty percent of it is still looking at abuse, addiction, that sort of thing. So it is a tough position to be in where we were trying to actually see the science move forward and yet because of the legal framework around it, it is so very difficult to do that. Much of the evidence we have right now is anecdotal, very hard to quantify, very hard to really put full credence in, and yet this is the best evidence available as these state laws have changed.
As I was listening to you, Mr. It is Conclusion My question now for the entire group is how do we move forward from here? If this conclusion of the National Academy committee is indeed pertinent, as I think it is, what do we do next?
I have a couple of comments. One of the areas that presents a barrier is the current requirement that all cannabis used in research come from a single source, which happens to be the University of Mississippi, supported through a contract with National Institute on Drug Abuse NIDA. We and others have been advocating for diversification of products and formulations, and the DEA in August, made a determination that it would be within the legal bounds of the international treaty that governs the control of substances Single Narcotic Convention to allow other sources to be licensed to provide cannabis for research purposes.
That could be extremely useful, since it would allow for a diversification of the inventory, and provide a clearer, more direct path for individuals who wanted to develop cannabinoid medications. Moreover, it would also be helpful for researchers to be able to obtain and analyze samples of what people are purchasing from dispensaries or growing themselves to determine positive or negative health outcomes of real-world products. The current Federal laws prohibit this, so it is a missed opportunity.
We are attempting to work with our federal partners to see if there are ways to address that. There is not a bias against funding good research on the potential therapeutic effects of cannabis or cannabinoids. NIDA's mission is mainly about abuse; however, we are still the largest funder of research to study the basic mechanisms of the cannabinoid system—with the potential to develop therapeutics and the therapeutic effects for pain and treatment of addictions using cannabidiol, for example.
Other NIH institutes fund work that falls within their mission—the National Cancer Institute or the National Institute of Neurological Diseases and Stroke are interested in cancer and epilepsy treatment, respectively. But most of what NIH funds are investigator-initiated research, so if we do not get good proposals, then we can't fund them. I agree with that point, and I think there has also been tremendous movement within the federal government, including the diversification of the supply.
That being said, it seems likely that movement will be slow, maybe even glacial, as it has been in years past. That history has made so many people, researchers, as well as activists and advocates, impatient.
One of the most astonishing recent developments is that Senator Orrin Hatch is now suddenly an advocate for removing the barriers to research.
He is somebody who is politically conservative and has antidrug credentials as strong as anyone could have. To me, that is, really where the solution is found is in Congressional action that sweeps those barriers away and lets research proceed in a way that it really should have been all along.
The question related to best ways to move this research forward is especially apropos given our political climate right now. And as somebody who is committed to studying both the therapeutic and the adverse effects of cannabis and cannabinoids, I have been dedicated to pursuing this research. I have thought about different ways to accomplish these goals.
One is to find alternate sources of funding, so not necessarily rely on NIDA, because their mission is to study substances of abuse, not necessarily the therapeutic effects.
In addition, to look at alternate sources of cannabinoids to understand the therapeutic potential of cannabinoids. For instance, studying different formulations of a cannabinoid-based product to answer some of the questions that are top of mind. Again, this is working within the framework and regulations that we have to deal with right now. I also think a lot about the importance of dissemination of findings.
There has been a great deal of interest in the media related to the strong epidemiological and state level findings, promoting research related to the pre-clinical data, as well as controlled human data that will help the public understand the issues related to the clinical utility of cannabis and cannabinoids. Another important avenue to pushing research forward is to actively reach out to investigators who might not necessarily be directly in the field of cannabis and cannabinoid pharmacology, but who are in clinical areas that are particularly important for understanding the potential therapeutic effects of cannabis and cannabinoids.
For instance, collaborating with clinician researchers in oncology, anesthesiology, and neurology would have a significant impact on the quality and generalizability of clinical studies. Finally, it is important for researchers in our field to understand and work with the regulatory hurdles.
These are just some of the things that we have to do to push research forward. I would like to throw in my two cents. It is not so much the regulatory hurdles. Those are there and may change, but they are what they are.
What concerns me most is the lack of clarity as to what one needs to demonstrate. As Graham Boyd pointed out before, one of the key criteria for a Schedule I drug is the lack of medical uses. The question is, what does Schedule I define as medical use? In the world of the FDA, we have a clear response to that question. New drug candidates have to go through a series of pre-clinical tests, Investigational New Drug IND application, and then clinical trials.
At the end of this process, you have your answer: But is this the same path that is required by the DEA to be able to say that? Because if it is, we have that answer already because THC, which is the main, if not the only, truly intoxicating component of cannabis, has gone through those very same studies, those I just mentioned.
Marinol is an FDA approved drug. This is where I am confused. There must be other criteria. What are those criteria? Where is it that our researchers need to aim to be able to address the medical value of cannabis? Maybe this is not a fair question to this group. I do not know if anybody has the answer. But maybe we do, so that is why I am raising it.
I would like to hear Graham's thoughts but the only thing that I would say is that I do not dispute anything you say, but when there is a petition to reschedule marijuana, the plant, the question immediately becomes what are you talking about.
Are you talking about a plant that is mostly THC, that is mostly CBD, that has unspecified different components in it? So you immediately get lost in that morass when you petition to reschedule the plant.
I would echo the point that I think one of the hurdles about cannabis is the fact that we are trying to schedule a whole plant.
We do not schedule the opiate plants, poppy—we do not schedule poppy. We do not schedule coca. This was not the case for marijuana and THC, because cannabis was placed in Schedule I legislatively, before dronabinol synthetic THC was approved as a medication. Okay, I stand corrected. I did not understand that there were any other plants, whole plants that got scheduled, which is a challenge I think for moving forward the medical—the categorization of the products that can come from the plant.
This is where I think the law and the way the law interprets itself is crucial because if indeed, say opium, is Schedule II, then also papaverine is Schedule II, and it is not.
Papaverine is a mild relaxant. It is a muscular relaxant that has been used and is still used in therapy, and it is not scheduled. The problem we see with cannabis is that we have a special situation where not just the plant itself is scheduled but each and every chemical component of the plant that goes under the cannabinoid rubric. You know, in the s, when the Controlled Substance Act was enacted, it could have made sense because at that time we did not know about the existence of cannabinoid receptors, and we did not know that these receptors are responsible for the totality of the effects of THC.
But we know that now. Some of the educational efforts that we scientists should put toward to the public and toward lawmakers are to explain that if there is one substance in cannabis that needs to be perused and needs to be considered carefully, that is THC, because that is the one that intoxicates people. And that particular substance at least in its synthetic form is in Schedule III. So anything else that does not intoxicate should not be scheduled at all. That is chemistry But I do not want to belabor the point.
Any other comments you would like to add at this point? In trying to make sense of the cannabis plant, its component parts, the various molecules that exist within the plant, whether they are naturally occurring or synthesized and trying to make sense of all of that, you feel like you have gone through the looking glass.
There is not anything that actually makes sense from a scientific point of view, from a legal or regulatory point of view.
On its own, a rat might work for five zaps of pleasure. With morphine in its system, it might work for ten. But if you give it CBD before giving it morphine, it will work for five, like it did with no drugs in its system.
If a specific serotonin receptor is blocked, CBD no longer has this effect. Since we know that CBD can directly stimulate serotonin receptors, this means that its ability to help treat addiction likely depends on its actions at serotonin receptors.
Building on animal research, pilot studies in humans have been conducted. At this stage, researchers evaluate the safety and side effects of treatments. In a double-blind, placebo-controlled phase I trial, CBD co-administered with fentanyl was well-tolerated and had no adverse effects. Basically, they gave heroin addicts a dose of CBD or placebo on three consecutive days.
They then showed them opioid-related or neutral video cues and measured cue-induced drug craving. CBD decreased cravings and anxiety at all time points. In other words, these small pilot studies in humans are consistent with animal research showing that CBD can diminish cravings and anxiety triggered by drug-associated cues.
This is key, because drug relapse in recovering addicts often follows exposure to such cues. Nonetheless, public approval of cannabis legalization has never been higher.
Part of the reason for this comes from research that has disproved time and time again that cannabis is not what the failed War on Drugs describes. For Stephen Mandile, the fight for legalization continues. Never standing down, Mandile spent several days and nights outside the Statehouse attempting to reach the lawmakers who could help him achieve reform. United States drug policies are the vehicle by which the opioid epidemic was injected into America.
There is nothing wrong with opioids, which have been used for thousands of years. The problem is prohibition that lends itself to irresponsible usage and bootleg products. Portugal decriminalized opioid use in and now has almost no overdose deaths. It is inappropriate to demonize opioids to make the case for cannabis. Thank you for making this important point! Think of what that could do for someone who needs opioids for their pain.
To your point about Portugal: In many states in the U. So we have a complicated comparison here with a lot of other details to unpack! But the impact of drug policy on consumer behavior is important, no doubt!
Hope that helps clear things up — appreciate you reading and weighing in. You also show 0 knowledge about addiction and of course—0 knowledge of understanding this article. This quote captures the description of Opioid addiction then continues on with real research that anyone using google scholar and pull up and understand if you are not already addicted to mind altering pharmaceuticals—especially the psychotropics.
Of the thousands of years that people have used opioids, the pharmaceutical industry has been around about The profiteers of the drug war include law enforcement, lawyers, physicians, addictionologists, hospitals, prison unions, and politicians. They have profited to the tune of hundreds of billions of dollars, and unlike the drug companies, they control both the legal system and medical care.
He agrees with me, not you. Your suggestion that my view might be based on drug use demonstrates the extent to which the drug war is a witch hunt, as Thomas Szasz described in Ceremonial Chemistry. Thank you guys for taking on the huge task of simply educating the public about how drugs interact with the body. I saw you do it for the cannabis industry and I love that you just put out an article about how cannabis can help with the opioid epidemic.
Obviously nothing has really worked in the past for treating an opiate addiction so we must try new things. This is a great first step towards starting to seriously consider CBDs to help with opiate addiction. Actually,, I do believe that the DEA just outlawed kratom a few days ago.. Here we have a plant that has the potential to assist people as they recover from opiate abuse or addiction and make that whole process easier on them and: What an insidious and disproportionate amount of power the dea has.
There was a lot of push back on this so they backed off a lot. No, they did not. They backed off because of public comments and are studying it more before deciding.
I next to study cocaine myth I read more for program? I have never experienced any pain relief from cannabis, and I have smoked a lot of cannabis. On one notable occasion I had a bike accident and suffered a compound fracture of my ankle. I was out in the countryside and all I had was 2 joints—-which I consumed while almost passing out from the pain.
The pot provided no relief whatsoever and I was in agonizing pain until the ambulance showed up 30 minutes later. Then—-I got some immediate pain relief from fentanyl on the way to the hospital and once there I received more opiates at the hospital.
Anyone who thinks that we can get rid of opiates and replace them with pot is not thinking clearly. I would not encourage anyone to falsely believe that pot will save them from severe pain; it will not.
At least not for me. You took the wrong strain and the wrong dosage. I have a condition called Porphyria and was born with it and as my body aged—so did my liver and other internal organs making me highly sensitive to pharmaceuticals and I literally died from a doctor prescribed pharmaceutica and was resusitated. A bout with polymyalgia like Fibromyalgia a few years ago and lowest dosage possible of Prednizone left me with neurological Dysphonia or inability for my vocal chords to produce sound in order to talk and now I must get a Botox shot every 3 months.
Oregon did not have legal medical marijuana, but my son found some for me and in total desperation and excruciating post surgery pain, I smoked it. It not only totally took care of my pain, but I actually stopped my nonstop vomiting and dry heaves for hours on end and actually could keep water and food down and had an appetite.
Not in my life even if I were diagnosed with cancer. You repeat the false claim that opioids are associated with dementia. There is no evidence supporting that. Well maybe you just think it is crazy to take opioids for Fibro because research has ruled them out as the drug of choice for this condition which causes chronic pain.
Better choices are cannabis, anti-seizure meds, muscle relaxants, cymbalta. My beloved German Shepherd Heidi was showing more and more weakened hip conditions and pain as she was born with Hip Displacia.
Cannabis and the Opioid Crisis
Protect Your Family from the Opioid Epidemic. With opioids like heroin and prescription pain pills ravaging our communities, take steps to. 6 days ago President Donald Trump promised as a candidate to “spend the money” to address the opioid epidemic, which is now the deadliest drug. Cannabis helps curb side effects post opioid dependence. Some experts say CBD: The new hype or a complete solution? But others express.