The Safety and Efficacy of Natural Medicine vs. Pharmaceutical Synthetics
The validity of any medical treatment can be determined by answering two very simple questions: Does it work? and Is it safe? And yet, assumption bias leaves us asking only one. We assume pharmaceuticals work and wonder if they are safe. We assume natural medicine is safe and wonder if it works. In order to accurately answer the dual questions of safety and efficacy we have to breakdown our long standing assumptions about both synthetic and natural medicines by examining:
How they function
How they are tested and regulated
Direct comparisons of established synthetic and natural medicine treatments for depression, anxiety and pain management
Safety by the numbers
Functionality: Is it Better to Treat the Symptom or the System?
Pharmaceutical drugs are designed to elicit a specific reaction via an introduced chemical interaction. The side effects are what manufacturers (and to a greater extent doctors and patients) consider the risk-benefit trade off. Natural or herbal medicines impart broad synergistic actions on physiological systems that while non-targeted support and hasten the bodies natural healing mechanisms. Let’s use a simple analogy to put the two approaches into perspective:
Synthetics: You wake up in the morning to a kitchen full of ants. You’re late for work and have no time to deal with the invasion so you set off a bug bomb and head out for the day. You’ll probably have to throw away some food and you’ll definitely have to wash the dishes and countertops but you’re confident the ants will be gone and you’re willing to accept the chemical cleanup as part of the risk-benefit trade off.
Natural Medicine: Now imagine the same scenario but rather than setting off a bug bomb you take a broader approach to improving the surrounding environment. Over the next few days you deep clean the kitchen, sweep the porch and spray a mixture of vinegar and water beneath the potted plants. The flow of ants becomes a trickle, the trickle becomes nothing.
In moments of acute pain (or need) the question, is it better to treat the symptom or the system? is valid but over the long-run it becomes rhetorical. Eliminating the root cause(s) of a condition while promoting the bodies natural healing capabilities is clearly a better permanent solution than introducing and maintaining foreign chemicals in your system.
Testing and Regulation: Complicated Does Not Equal Competent
We know that the FDA approval process is long and arduous. We know that all new drugs are thoroughly vetted.
We don’t know what we know.
FDA approval is a five-step process:
Discovery and Development
Preclinical Research
Clinical Research
FDA Review
FDA Post-Market Safety Monitoring
The FDA has zero involvement (aside from pre-set guidelines) until step-four of the approval process. All preclinical and clinical testing is done independently by pharmaceutical manufacturers and often on the basis of relatively short-term studies. Neither the FDA nor any third-party laboratory directly tests new synthetics. The proof is in the paperwork and proof is in question.
A recent study conducted by the Mayo Clinic’s Evidence-Based Practice Center found that the results from new clinical trials are significantly more pronounced than the results shown in later trials. Researchers demonstrated that the recorded effects from the first or second study reviewing a new treatment was 2.67 times larger than the recorded effects in subsequent trials. And lead researcher Doctor Fares Alahdab was quoted as saying, “This phenomenon of exaggerated early results was present in a whopping 37 percent of the studies we reviewed.” The research team refers to this trend as The Proteus Effect. Side note: Proteus was a shape-shifting prophet from Greek mythology; difficult to catch and harder to trust.
Natural medicine (botanicals) are not subject to the FDA’s five-step approval process because they are not classified as medicine. The FDA labels all natural medicine as dietary supplements. The classification is a question of testability not efficacy.
As stated above, natural medicine heals via a multi-pronged approach to overall wellness. The chemical composition of natural substances is only one facet in a larger holistic healing process that includes emotional, mental and spiritual considerations. Critics eager to fit natural medicine into the same chemistry set as its pharmaceutical counterpart will say that herbal derived remedies need to be assessed of their pharmacological qualities and safety via new biologic technologies like pharmacogenomic and microarray methodology. Aside from the fact that any such testing would disregard the aforementioned holistic components, it’s a question of scale. Big pharma spends billions on research and development and Mom-and-Pop natural medicine producers simply don’t have those kind of resources. Until a comprehensive testing structure that incorporates all elements of the traditional medicine system(s) is defined and implemented, the FDA will continue to monitor natural medicine via supplement manufacturing protocols which include quality standards and labeling restrictions. While toxicity issues from medicinal plants are exceptionally rare, reported cases are typically due to misidentification of plants in the form in which they are sold, or incorrect preparation and administration by improperly trained providers, so a certain level of consumer based research and supplier vetting is required.
So, who protects the public when post-market problems arise? The public.
The FDA has the ability and responsibility to pull dangerous products from the market but they rely on manufacturers, medical professionals and consumers to report potential issues. The reporting systems are separate but equal in terms of functionality. For approved pharmaceuticals all concerned parties are encouraged to use the FDA’s Adverse Events Reporting System (FAERS) and for natural medicine, or dietary supplements, concerns can be registered through the FDA’s Safety Reporting Portal.
Let’s embrace the role of concerned consumer and take a closer look at the safety and efficacy of pharmaceuticals and natural medicine as treatments for depression, anxiety and pain management.
Depression & Anxiety: The Safety and Efficacy of Common Treatments
Anxiety disorder is the most common mental illness in the US affecting more than 40 million adults annually. It is a complex issue with chemical, emotional and lifestyle considerations. Aside from cases of acute clinical depression it seems to be a perfect fit for a natural, whole system approach to healing and yet 12.7% of the U.S. population is currently taking doctor prescribed antidepressants. Within that group, 68% have been taking the drugs for more than two years and 25% for a decade or more. The consequences of defaulting to synthetic medications is alarming.
Benzodiazepines (Xanax, Valium, Restoril): are a commonly prescribed short-term treatment for depression and anxiety. They are powerful sedatives that increase the effect of a brain chemical called GABA (gamma amino butyric acid) which reduces activity in the part of the brain responsible for rational thought, memory and emotions. In other words, they reduce depression and anxiety by turning the volume way down. The side effects include weight gain, decreased sexual desire/ability, difficulty concentrating and ironically depression. The initial signs of benzodiazepine dependence can appear within a little as one week and withdrawal symptoms can last anywhere from a few days to a few months.
Selective Serotonin Reuptake Inhibitors (SSRIs): are the most commonly prescribed long-term treatment for depression and anxiety. They block the reabsorption (reuptake) of serotonin in the brain thus increasing the level of serotonin available. Depression has been linked to low levels of serotonin, but whether this contributes to depression or results from it remains unclear. It is also unclear what the long-term effects of serotonin manipulation may be. While SSRIs such as Prozac, Paxil and Zoloft are not considered additive, ending treatment may result in withdrawal like symptoms (or discontinuation syndrome.)
The mood altering and addictive properties of benzodiazepines makes them an obvious no-go for long-term treatment of depression and anxiety. And SSRIs are a perfect example of the Proteus Effect referenced above. When SSRIs were initially released in the early 1990’s manufacturers were touting sky high rates of effectiveness. Subsequent studies have chipped away at those numbers to the point that it’s now debatable whether or not SSRIs are any more effective than a placebo. Consider this snippet from a New York Times article entitled: Do Antidepressants Work?
It’s not that we lack research. Many, many studies of antidepressants can be found in the peer-reviewed literature. The problem is that this has been a prime example of publication bias: Positive studies are likely to be released, with negative ones more likely to be buried in a drawer.
In 2008, a group of researchers made this point by doing a meta-analysis of antidepressant trials that were registered with the Food and Drug Administration as evidence in support of approvals for marketing or changes in labeling. Companies had to submit the results of registered trials to the F.D.A. regardless of the result. These trials also tend to have less data massaging — such as the cherry-picking of outcomes — than might be possible in journals.
The researchers found 74 studies, with more than 12,500 patients, for drugs approved between 1987 and 2004. About half of these trials had “positive” results, in that the antidepressant performed better than a placebo; the other half were “negative.” But if you looked only in the published literature, you’d get a much different picture. Nearly all of the positive studies are there. Only three of the negative studies appear in the literature as negative. Twenty-two were never published, and 11 were published but repackaged so that they appeared positive.
The 50/50 odds versus a placebo were backed up by the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial which was carried out over a period of six years at a cost of $35 million USD. The study sought to test the effectiveness of both pharmacotherapy and cognitive therapy in order to determine whether certain treatments are more optimal after one or more failed trials. Put simply: Which is more effective, SSRIs or conversation, emotional regulation and coping strategies? Across all tested groups, including those who received a combination of treatments, remission ranged from 18%-30% and there was no difference in effectiveness between any treatments at any treatment level.
St. John’s Wort: a separate study with a nearly identical sample size to the STAR*D trial was conducted to test the effectiveness of St. John’s Wort versus SSRIs. St. John’s Wort is a plant with yellow star shaped flowers that grows globally in areas with a sunny, dry climate. It has a positive effect on mood and depression management via a chemical compound called hyperforin. Here is what the study found:
St John’s wort extract did not differ from SSRIs in clinical response, remission, and mean reduction in Hamilton Rating Scale for Depression score.
St John’s wort extract had a significantly lower rate of adverse events compared to SSRIs and had fewer withdrawals due to adverse events.
St John’s wort extract had superior safety in the management of patients with depression.
Conclusion Both St John’s wort extract and SSRIs are effective in treating mild-to-moderate depression. St John’s wort extract is safer than SSRIs.
Psilocybin Treatment as an SSRI Alternative in Cancer Patients
Generalized anxiety and Major Depressive Disorder (MDD) are extremely prevalent in cancer patients. Oncologists are hesitant to prescribe Benzodiazepine or SSRI treatment due to the high risk of negative treatment interactions and serious questions about efficacy. ClinicalTrails.gov provides a neat summation of the issues:
Optimal therapy of MDD in cancer patients remains uncertain. Very few placebo controlled trials have been performed in this population, and there is currently no uniformly accepted standard of care. Some of the evidence from studies in depressed but otherwise medically healthy patients may be applicable to cancer patients, but there are several factors which complicate the treatment of depression in this group. For example, the overlap of symptoms between depression and the underlying malignancy can confound the diagnosis. Simultaneous treatment of the underlying malignancy introduces adverse effects from surgery, chemotherapy, or radiation, as well as an increased likelihood of drug-drug interactions. Finally, co-morbid conditions such as cancer pain can contribute to the depression, requiring simultaneous therapy. As a result of these unique factors, the treatment of MDD in cancer patients cannot necessarily be approached using the standard recommendations for the general population.
There is scant evidence supporting the effectiveness of pharmacologic therapy in cancer patients with MDD. In the last 25 years only four placebo controlled trials have been published, and of these only two have shown a statistically significant improvement in depression scores with active treatment.
Given the uncertain and delicate nature of MDD treatment in cancer patients, oncologists and researchers are understandably searching for alternative treatments. Psilocybin (naturally occurring psychedelics) have shown promising results.
At Johns Hopkins, the effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction.
The John Hopkins trial proved the efficacy of psilocybin but how did psilocybin compare to antidepressants in terms of safety? The study stated that, “No serious adverse events attributed to psilocybin administration occurred.” A low percentage of patients experienced nausea and mildly elevated blood pressure but none of the reported issues required medical intervention and all were fully resolved by the end of the session.
Can Cannabis Help Us Wean Off of Opioids?
The opioid crisis is not a modern phenomena, it’s the result of aggressive mis-marketing on the part of pharmaceutical manufacturers that dates back more than a century. Morphine was hailed as a miracle drug and embraced by the medical community for everything from toothaches to chronic pain until it was proven to be extraordinarily addictive. Heroine was intended to be a safe morphine alternative and was initially marketed as a cough and cold remedy for children but was soon revealed to be even more addictive than its predecessor. In 1996, OxyContin became the latest and arguably most damaging of the opioid miracle drugs. In response to mismarketing and blatant suppression of the drug’s addictive properties, 48 states have filed lawsuits against Purdue Pharma for their ongoing role in the opioid crisis.
Effective pain management, especially in regards to chronic and severe pain, is a medical necessity but the opioid crisis has emphatically proven that history can and will repeat itself. We can’t fall for/allow for another mismarketed “miracle” from the pharmaceutical community. We have to demand a better, safer alternative.
Cannabinoids, the chemical compounds found in the Cannabis plant, have proven effective in basic experiments on pain. Our nerve endings contain a high level of receptors which interact with cannabinoids to block peripheral pain. Researchers compared the effects of a single potent dose of THC cannabinoids with the pharmaceutical pain reliever codeine. 10 milligrams of THC provided the same pain relief as a 60-milligram dose of codeine and 20 milligrams of THC worked as well as 120 milligrams of codeine. THC used at elevated levels produced more of a sedating effect but patients also reported feeling a greater sense of well-being and reduced anxiety as compared to the effects of codeine.
There are correlating statistics suggesting that providing pain sufferers with an alternative via legalized marijuana leads to a decrease in opioid usage. A study analyzing Medicaid prescription data from 2011 to 2016 showed that states with legal marijuana laws have seen a 5.88% lower rate of opioid prescriptions and that number rose to 6.38% when recreational use data was included. In study authors noted:
“We do not know whether patients actually avoided or reduced opioid use because of increased access to cannabis (marijuana).” However, given that millions of prescriptions for opiates were not written, and consequently there were millions fewer bottles of prescription opiates consumed, sold, diverted, or abused, it does not seem to be too big a leap to infer that opiate use was avoided, or at least reduced.
Cannabis has proven to be effective as a mild-to-moderate pain reducer, and as a non-addictive substance it is safe for long-term use, that said, we have to be careful about switching one miracle for another. In cases of severe pain and trauma we are (at least temporarily) stuck with opioids but for chronic and recovery phase pain management, we have to find a non-opioid solution. Cannabis may be the best available alternative.
Safety by the Numbers
We’ve become desensitized to the adverse effects of synthetic medications. We watch the polished commercials and wait for the punchline; thirty seconds of side-effects. These pervasive marketing campaigns have bludgeoned us into accepting an unbalanced risk-benefit tradeoff.
Every year there are approximately 2.2 million hospitalizations due to adverse pharmaceutical drug reactions, resulting in 100,000 deaths per year and those are just the direct toxicity numbers. Those figures don’t take into account pharmaceutical drug related injuries such as elderly patients falling and hurting themselves due to adverse prescription interactions. There is no punchline to this pharmaceutical reality. We have to be more cognizant of the safety and the risk-benefit tradeoff of prescribed medications especially given that effective natural medicine(s) are an available alternative. Life threatening reactions to herbal supplements is extremely low with annual reported deaths of 12-24 cases, typically due to negative interactions with restricted substances such as alcohol.
Let’s look at liver toxicity as an isolated example. Antidepressants are responsible for 2%-5% of all clinically apparent cases of drug induced liver injury and over the years several antidepressants have been pulled due to complications with hepatotoxicity. Most recently, Nefazodine in 2003 after multiple reports of acute liver failure. On the other hand, Kava root (a proven natural remedy for stress & anxiety) has been shown to be far safer than synthetic antidepressants with a reported liver injury rate of less than 1: 1,000,000 daily doses—essentially non-existent.
When it comes to your health there is no choosing sides, the best available balance between safety and efficacy is the only requirement that matters. Challenge assumptions about natural medicine, challenge the easy acceptance of synthetics and consider what is best for your long-term health. Our bodies are incredibly adept at healing themselves. With a holistic, natural approach to healthcare management, you’ll find that a pillbox is rarely needed.