EXPOSE on CBD Part 2: Take Care with This Cannabinoid - The Problem of Pain

Expert Insights, Latest Addiction Research, Mental Health Intersection, News, Syndicated

EXPOSE on CBD Part 2: Take Care with This Cannabinoid – The Problem of Pain

August 15, 2024October 20, 2024By WRD News Team

The placebo effect is a fascinating phenomenon where a person experiences real changes in their health after receiving a treatment that has no therapeutic value. This effect is particularly notable in pain management.

When a person believes they are receiving a pain-relieving treatment, their brain can release natural painkillers called endorphins. These chemicals interact with the brain’s pain pathways, reducing the perception of pain. This process is known as placebo analgesia.

Research has shown that the placebo effect can be as effective as actual pain medications in some cases. For instance, studies have found that patients receiving a placebo can experience pain relief comparable to those taking low doses of morphine. This effect is not just about positive thinking; it involves complex neurobiological reactions, including increased activity in brain regions associated with mood and self-awareness.

The understanding of what the placebo effect looks and manifests as, is clearly evident in many clinical settings, and it would appear very much part of the recent cannabis phenomenon. However, deliberately harnessing and maintaining this potential clinical tool is at best unpredictable.

When it comes to cannabis, the problem is that we need to create the placebo effect whilst disconnecting the patient from the substance that may have many other negative side-effects beyond the pain issue, which cannabis most certainly has.

In a 2022 article in the ‘Conversation’ , this issue was again raised as research had concluded that the placebo effect around cannabis was considerably high, due in part to the psycho-social zeitgeist generated around this substance for the last 30 years in all sectors of the public square.

There are numerous examples of the relationship between treatment expectations and placebo responses. If a person thinks they will experience relief from their pain by using a certain product or treatment, this can change the way they end up perceiving incoming pain signals – making them think their pain is less severe. Recent evidence suggests that the placebo effect may work even if we’re presented with evidence that contradicts our initial expectations.
We cannot say with 100% certainty that media coverage is responsible for the high placebo response observed in our review. But given placebos were shown to be just as good as cannabis for managing pain, our results show just how important it is to think about the placebo effect and how it can be influenced by external factors – such as media coverage. For treatments, such as cannabinoids, that receive a lot of media attention, we need to be extra rigorous in our clinical trials.

If one could excise the cannabis from the ‘Cannabis placebo’ influence, then we may potentially be able to generate a sustainable pain-management system for some of the affected population without all the toxic side-effects of this genotoxic and neurotoxic substance – Ah, but we digress.

In part two of our CBD Expose, we are drilling down more into its use, impact and problems with cannabis and pain.

A ‘Punch’ to your System, but No ‘Bang’ for your Buck?

CBD has garnered extensive attention for its alleged health benefits, particularly in pain relief. However, the reality is that the efficacy of CBD products can be highly variable, and their safety is often questionable. A comprehensive review from The Journal of Pain highlights several critical issues.

Firstly, there is substantial inconsistency in the actual CBD content of products available in North America and Europe. Some products contain no CBD at all, while others have significantly more than what is advertised. This variability poses a direct risk to consumers, as the unregulated nature of these products can lead to unexpected side effects. Additionally, many CBD products contain other potentially harmful chemicals that have been reported to cause serious health issues in children, adults, and the elderly alike.

A task force by the International Association for the Study of Pain (IASP) reviewed 16 randomised controlled trials (RCTs) on the use of pharmaceutical CBD for various pain conditions. These studies covered 12 different pain states and utilised oral, topical, and buccal/sublingual administration methods, with doses ranging from 6 to 1,600 mg over treatment periods from a single dose to 12 weeks. Shockingly, 15 out of these 16 trials showed no significant benefit of CBD over a placebo. This finding underscores the ineffectiveness of CBD in pain management and questions the validity of its widespread use.

The safety profile of CBD is equally concerning. While small clinical trials using verified CBD suggest it may be relatively benign, large-scale evidence indicates growing rates of serious adverse events and hepatotoxicity linked to CBD use. The Food and Drug Administration (FDA) in January 2023 stated the need for a new regulatory pathway for CBD, emphasising that consumers and healthcare providers should rely on evidence-based information rather than advertisements. Given these findings, it is clear that CBD for pain is not only ineffective but also potentially harmful and expensive.

Medical cannabis use for chronic pain has also been linked to cardiovascular risks. A nationwide study published in the European Heart Journal found that people taking medical cannabis for chronic pain had a slightly increased risk of arrhythmia—conditions where the heart beats too slowly, too quickly, or irregularly.

The study analysed data from 5,391 Danish patients prescribed cannabis for chronic pain and compared it with 26,941 patients with chronic pain not receiving cannabis. The results showed a 0.8% risk of arrhythmia diagnosis within 180 days for cannabis users, more than double the risk for non-users. The risk was notably higher among patients aged 60 and older and those with preexisting cardiometabolic diseases.

These findings suggest that while medical cannabis may offer some pain relief, it also carries significant cardiovascular risks that require careful monitoring, particularly in patients already at risk for heart conditions. More research is needed to fully understand the long-term cardiovascular effects of medical cannabis.

Meta-analyses and ongoing clinical research consistently highlight the limited value of cannabis for pain management. A meta-analysis of 20 studies involving 1,459 individuals found that the reduction in pain attributed to cannabinoids was not significantly better than a placebo. This finding is crucial because it suggests that the perceived benefits of cannabis may be largely due to the placebo effect rather than any pharmacological action.

Moreover, the meta-analysis revealed that the high media attention and positive bias towards cannabis do not correlate with improved clinical outcomes. This discrepancy raises concerns about the influence of media hype on patient expectations and the potential for placebo responses to shape future clinical trials.

The recommendation against prescribing medicinal cannabis for chronic non-cancer pain outside of registered clinical trials is one of the most unambiguous and evidence-based statements in recent literature. Despite the decades-long declaration of cannabis as a panacea, the promises of its therapeutic potential remain largely unrealised. Current evidence either fails to support the use of cannabinoid products for CNCP or is of such low quality that no valid scientific conclusions can be drawn.

In Australia and New Zealand, cannabis-derived products are now available for therapeutic use, with chronic pain being the most common reason for their prescription. However, more than 90% of Special Access Scheme – Category B (SAS-B) approvals for chronic pain lack robust evidence of consistent benefit. Cannabidiol-only formulations, the most commonly prescribed type, have never been the subject of a published randomised controlled trial (RCT) for pain indications.

Moreover, there are documented harms associated with cannabis use, particularly its sedative effects, interactions with other medications, and neuropsychiatric effects. Given these concerns, the clinical use of cannabinoid products cannot be ethically recommended outside a properly established and registered clinical trial environment until high-quality evidence is available.

The integrity and trustworthiness of research on cannabis and pain management are paramount. A recent investigation into the veracity of published trial data on spinal pain revealed significant concerns. Ten trials were systematically identified and assessed for risk of bias and trustworthiness using the Cochrane risk-of-bias tool and the Cochrane Pregnancy and Childbirth group’s Trustworthiness Screening Tool.

The findings were troubling: eight out of ten trials reported results divergent from the evidence base, raising questions about research governance, data plausibility, and apparent data duplication. These discrepancies reduce confidence in the validity of the trials and suggest that such studies should not inform systematic reviews, clinical training, policy documents, or any relevant instruction regarding adult chronic pain management.

This highlights the need for rigorous research standards and transparency in the study of cannabis and its potential therapeutic effects. Without such standards, the evidence base remains unreliable, and the purported benefits of cannabis for pain management remain unproven

Swapping Out the Pain Meds – How does Cannabis Fair?

The notion of using cannabis as a substitute for opioid painkillers has gained traction, particularly in light of the opioid epidemic. However, evidence from the National Academy of Sciences and the International Association for the Study of Pain indicates that substituting opioid treatments with cannabis is fraught with risks.

Studies comparing opioid mortality rates in states with and without marijuana legalisation found that the rates increased more rapidly in states that had legalised marijuana. This trend was consistent across various demographics, with non-Hispanic blacks and Hispanics experiencing the most significant increases in opioid-related deaths. These findings suggest that rather than mitigating the opioid crisis, marijuana legalisation may have exacerbated it.

Additionally, a national epidemiologic survey revealed that nonmedical prescription opioid use and opioid use disorder significantly increased within three years of cannabis use. This alarming trend challenges the hypothesis that cannabis can serve as a safe and effective alternative to opioids for pain management.

Beyond that, research is finding that combining cannabis with opioids for pain management is associated with increased mental health issues. A study from the University of Houston found that adults who mixed these substances reported higher levels of anxiety, depression, and substance abuse issues compared to those using opioids alone. The study surveyed 450 adults with moderate to severe chronic pain and revealed that co-users had elevated symptoms without experiencing additional pain relief.

These findings underscore the complexity of managing chronic pain with multiple substances and highlight the need for integrated treatment approaches that address both mental health and pain. As we’ve seen in this above, the co-use of cannabis and opioids poses risks that must be clearly warned against by healthcare providers to ensure holistic and effective patient care.

As we have seen here, the co-use of opioids and cannabis among adults with chronic pain presents many challenges. Further research published in the Journal of Addiction Medicine suggests that combining these substances is associated with elevated anxiety and depression symptoms, as well as increased use of tobacco, alcohol, cocaine, and sedatives. Importantly, this co-use did not result in significantly better pain relief compared to opioid use alone.

These findings highlight a vulnerable population of polysubstance users with chronic pain, indicating the need for comprehensive assessment and treatment strategies that address both pain and the potential for substance misuse. The intersection of chronic pain, mental health, and substance use requires a multifaceted approach to ensure patients receive effective and safe care.

And the Specialists Say….?

The International Association for the Study of Pain (IASP) has taken a firm stance in light of insufficient evidence supporting the use of cannabinoids, including CBD, for pain treatment. After a comprehensive review spanning two and a half years, the IASP concluded that the clinical evidence does not meet the threshold required to endorse the general use of cannabinoids for pain control.

Andrew Rice, chair of the IASP’s Presidential Task Force on Cannabis and Cannabinoid Analgesia, emphasised that while the organisation does not dismiss the personal experiences of individuals who report pain relief from cannabinoids, more rigorous and robust research is needed. This research should focus on identifying which patients might benefit from cannabinoids, determining appropriate doses, and establishing optimal delivery methods. Until such evidence is available, the IASP cannot support the general use of cannabinoids for pain management.

The National Institute for Health and Care Excellence (NICE) has issued draft guidance that strongly advises against the use of tetrahydrocannabinol (THC) or mixtures of cannabidiol (CBD) and THC for chronic pain management outside of clinical trials. This recommendation also applies to severe treatment-resistant epilepsy. NICE’s position is based on the current state of research, which is limited and often of low quality. Clinical trials have shown a high incidence of adverse events, further complicating the case for CBMPs.

NICE’s guidance highlights the need for more robust research to evaluate the efficacy and safety of CBMPs for various conditions. The organisation refrained from making recommendations against the use of these products entirely, as such a move might hinder ongoing research and the potential benefits that some patients currently experience. However, NICE emphasised that the potential benefits of CBMPs are small compared to their high and ongoing costs, rendering them an ineffective use of National Health Service (NHS) resources.

Moreover, NICE’s draft recommendations specify that initial prescriptions for CBMPs should only be issued by specialists registered with the General Medical Council, although subsequent prescriptions can be managed by other prescribers under a shared care agreement. This cautious approach underscores the need for specialised oversight and the importance of continued research to validate the therapeutic claims of medical cannabis.

These specialist concerns in the U.K. have not stopped the now quasi-legitimate ‘vote for medicine’ practitioners from prescribing their panacea for pain.

The opening of the Medical Cannabis Clinic (MCC) in Manchester (UK) has sparked significant controversy within the medical community. The clinic, which aims to provide cannabis-based treatments for chronic pain and other conditions, has been accused of making unfounded claims about the drug’s pain-relieving qualities. Despite the clinic’s optimistic assertions, the Royal College of Physicians has stated that there is no robust evidence to support the use of cannabis for pain management.

Medical professionals have expressed deep concerns about the clinic’s practices, noting that its establishment appears to be driven by commercial interests rather than solid scientific evidence. Dr. Barry Miller, dean of the Faculty of Pain Medicine, highlighted the lack of reliable data supporting the efficacy of cannabinoids for pain and criticised the opening of such clinics before the publication of comprehensive research findings by the National Institute for Clinical Excellence.

Furthermore, the Medical Cannabis Clinic’s affiliation with European Cannabis Holdings, a company that promotes various cannabis products, has raised additional ethical questions. Critics argue that the clinic’s claims and promotional activities may mislead patients and healthcare providers, potentially contributing to inappropriate prescribing practices and overlooking the risks associated with cannabis use.

In Australia, the use of medicinal cannabis for chronic pain has been met with scepticism from leading pain specialists. The Faculty of Pain Medicine at the Australian and New Zealand College of Anaesthetists (ANZCA) advises against prescribing currently available cannabinoid products for chronic non-cancer pain outside of registered clinical trials. The recommendation is based on the lack of robust evidence from gold-standard studies proving the efficacy of these products.

Professor Michael Vagg, Dean of ANZCA’s pain medicine faculty, pointed out that existing medicinal cannabis products are not even close to demonstrating effectiveness in managing complex chronic pain. This cautionary stance is reinforced by the Therapeutic Goods Administration (TGA), which, despite approving numerous cannabinoid scripts, acknowledges that only a small fraction of chronic pain patients might benefit from medicinal cannabis, while many others may experience adverse side effects.

Media Hype and the Placebo Reality

The relationship between media hype and the placebo effect is a critical factor in understanding the public’s perception of cannabis for pain relief. Numerous studies have shown that if individuals believe a treatment will relieve their pain, this expectation can alter their perception of pain, making it seem less severe. This placebo effect can persist even when presented with contradictory evidence, underscoring the powerful influence of belief and expectation.

The unusually high media attention surrounding cannabinoid trials, often with a strong positive bias, may uphold high expectations and shape placebo responses in future trials. This phenomenon can complicate the interpretation of clinical trial results and suggests that some of the perceived benefits of cannabis for pain relief may be attributable to psychological factors rather than the substance itself.

This is borne out in the following Australian example.

A recent high-quality study led by the Mater hospital and the University of Queensland has provided critical insights into the effectiveness of cannabidiol (CBD) oil for palliative care patients with advanced cancer. The double-blinded trial, involving 144 patients, aimed to assess the impact of CBD oil on pain, depression, anxiety, and overall quality of life. Unfortunately, the study found no detectable effect of CBD on any of these parameters.

Despite the lack of symptom relief, the researchers called for more targeted trials to explore the potential benefits of medicinal cannabis further. The study highlighted that while CBD is popular for its non-psychoactive properties, it did not improve the specific symptoms evaluated in this trial. Yet again, this finding underscores the necessity of rigorous scientific evaluation before endorsing CBD or other cannabis-based products for medical use.

The study also noted that a significant portion of participants chose to purchase medicinal cannabis products after the trial, even though they were unaware of whether they had received CBD or a placebo. This behaviour reflects the social phenomenon surrounding medicinal cannabis, driven by high expectations rather than empirical evidence. While some patients may report benefits, the current evidence does not robustly support the widespread use of cannabis for chronic pain or other medical conditions. Rigorous, high-quality research remains essential to validate therapeutic claims and ensure patient safety.

A Conclusion

As we have touched on repeatedly in this overview of evidence and experience the constant call for proper, full, robust and thorough clinical trials was demanded. However, as we have written in previous articles the ‘called for research’ has been done and it’s still coming up negative.

What is also essentially unknown by almost all, is that since around 1997 up until March 2024 there have been 11,420 studies conducted on Cannabis THC alone, (not including Cannabis CBD or other cannabinoids) at a cost of $4.877 billion (USD) and the very best we can come up with from all this promised panacea of all ills is essentially the same therapeutics that were already available for prescription, with the exception of the newest pharmaceutical Epidiolex ®

Wilful ignorance aside, it is time that those charged with ensuring best practice in public health be accountable, stopped listening to freshly spun ‘old wives’ tales’ and let the science inform their practices and policies. As we saw with Big Tobacco, we are now seeing again with Big Cannabis – a relentless push by an addiction for profit industry that has tricked people into believing they are ‘feeling better’, but they are only getting worse.

Will it take another 30 years before the penny drops and then the class actions start?

The very disturbing tragedy in all this, is that the genotoxic harms of this hyped product will ripple into generations to come regardless of retroactive responses, and the black hole that is public health expense will just get deeper and darker.

WRD News Team