Our Proposal
We propose an integrated program of five holistic/alternative modalities, including the following two (Cannabinoid therapy and REST/Floatation therapy) be applied and studied toward reduction of opiate dependence and it’s complications and to identify and describe potential pharmacological and non pharmacological treatment options, including further non-opioid pharmacological treatments for acute and chronic pain management, along with patient communication and education regarding the risks and benefits associated with each of these available options.
Cannabis vs. Opioids
A University of Michigan March 2016 study published in the Journal of Pain provides some
compelling data. They found that cannabis:
• Decreased side effects from other medications
• Improved quality of life
• Reduced use of opioids (on average) by 64%
"We are learning that the higher the dose of opioids people are taking, the higher the risk
of death from overdose,” said Dr. Daniel Clauw, one of the study’s researchers and a
professor of pain management anesthesiology at the University of Michigan Medical School.
“[The] magnitude of reduction in our study is significant enough to affect an individual's
risk of accidental death from overdose."
Don Abrams, MD, a University of California-San Francisco researcher and clinician who brings a
rational approach to Cannabis use, is to be credited for forging another path forward in the use
of medical marijuana. Although a placebo-controlled study previously showed that oral Δ-9-THC
(dronabinol/Marinol®) in patients using opioids augments analgesia,1 this is the first human
study to show that inhaled cannabis safely potentiates the analgesia of opioids. The effect
does not appear to be pharmacokinetic (PK); rather Abrams and authors speculate that the
potentiation of analgesia is due to pharmacodynamic (PD) activity. However, previous studies
have demonstrated that THC and cannabidiol (CBD) enhance the penetration of other
drugs into the brain.2 In the case of a more complex Cannabis extract that would contain the
naturally occurring terpenes (eg, Β-caryophyllene) this could also enhance the THC (and other
cannabinoids) penetration of the blood-brain barrier as this is a general property of terpenes.
3,4,5
Several studies have shown that morphine and THC share many pharmacological
properties, including analgesia, hypothermia, respiratory depression, locomotor depression,
and tolerance development, even though the mechanisms of action of these 2 compounds are
quite different.6 More recently, a bidirectional cross-tolerance between morphine and THC has
been demonstrated in mice.7 Not surprisingly, synergic activities have been demonstrated
between cannabinoids and opioids, resulting in significant antinociception.8,9 Besides the
distinct cannabinoid and opioid receptors that colocalize in areas of the brain that process pain
signals, THC (and possibly other cannabinoids) induce the release of endogenous
opioids and endocannabinoids.10 These activities could account for PD synergic activity.
The limitations of the study include low participant number and lack of placebo control
(vaporizing a placebo would be extraordinarily challenging). Also it would have been interesting
to know the ratio of THC/cannabidiol (CBD). The THC concentration is given as 3.6% (in today’s
medical marijuana culture this is a low value). However the CBD concentration is not known,
and this compound may be effective in pain.11,12
Addiction and tolerance to opioids represent a major problem in clinical medicine. It is ironic that
another controlled substance may be useful for the tolerance and withdrawal symptoms that
develop from chronic use of opioids. Tetrahydrocannabinol and Cannabis spp. have also been
shown to be useful for the tolerance that develops from chronic use of opioids,14,15 as well as
some of the withdrawal symptoms (murine model).16
References
1. Narang S, Gibson D, Wasan AD, et al. Efficacy of dronabinol as an adjuvant treatment for
chronic pain patients on opioid therapy. J Pain. 2008;9(3):254-264.
2. Reid MJ, Bornheim LM. Cannabinoid-induced alterations in brain disposition of drugs of
abuse. Biochem Pharmacol. 2001;61(11):1357-1367.
3. Liu R, Zhang L, Lan X, et al. Protection by borneol on cortical neurons against oxygenglucose
deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through
nuclear transcription factor kappaappaB signaling pathway. Neurosci. 2011;176:408-419.
4. Nokhodchi A, Sharabiani K, Rashidi MR, Ghafourian T. The effect of terpene concentrations
on the skin penetration of diclofenac sodium. Int J Pharm. 2007;335(1-2):97-105.
5. Tas C, Ozkan Y, Okyar A, Savaser A. In vitro and ex vivo permeation studies of etodolac from
hydrophilic gels and effect of terpenes as enhancers. Drug Deliv. 2007;14(7):453-459.
6. Rapaka RS, Sorer H. Discovery of Novel Opioid Medications. Rockville, MD: National
Institute on Drug Abuse;1994.
7. Thorat SN, Bhargava HN. Evidence for a bidirectional cross-tolerance between morphine and
delta 9-tetrahydrocannabinol in mice. Eur J Pharmacol. 1994;260(1):5-13.
8. Vigano D, Rubino T, Vaccani A, et al. Molecular mechanisms involved in the asymmetric
interaction between cannabinoid and opioid systems. Psychopharmacol. 2005;182(4):527-536.
9. Cox ML, Haller VL, Welch SP. Synergy between delta9-tetrahydrocannabinol and morphine in
the arthritic rat. Eur J Pharmacol. 2007;567(1-2):125-130.
10. Welch SP. Interaction of the cannabinoid and opioid systems in the modulation of
nociception. Int Rev Psychiatry. 2009;21(2):143-151.
11. Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of
inflammation on oxidative stress. Free Radic Biol Med. 2011;51(5):1054-1061.
12. Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis
constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and
neuropathic pain. Eur J Pharmacol. 2007;556(1-3):75-83.
13. Wang J, Christo PJ. The influence of prescription monitoring programs on chronic pain
management. Pain Physician. 2009;12(3):507-515.
14. Vigano D, Rubino T, Parolaro D. Molecular and cellular basis of cannabinoid and opioid
interactions. Pharmacol Biol Behav. 2005;81(2):360-368.
15. Cichewicz DL, Welch SP. Modulation of oral morphine antinociceptive tolerance and
naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. J Pharmacol Exp
Ther. 2003;305(3):812-817.
16. Lichtman AH, Sheikh SM, Loh HH, Martin BR. Opioid and Cannabinoid Modulation of
Precipitated Withdrawal in Δ9-Tetrahydrocannabinol and Morphine-Dependent Mice. J
Pharmacol Exp Ther. 2001;298(3):1007-1014.
Below is the list of state approved indications for Medical Cannabis use within the state of
Illinois.
Cancer, glaucoma, HIV/AIDS, hepatitis C, ALS, Crohn disease, agitation related to Alzheimer
disease, cachexia/wasting syndrome, muscular dystrophy, severe fibromyalgia, spinal cord
disease (including but not limited to arachnoiditis), Tarlov cysts, hydromyelia syringomyelia,
rheumatoid arthritis, fibrous dysplasia, spinal cord injury, traumatic brain injury and
postconcussion syndrome, MS, Arnold-Chiari malformation and syringomelia, spinocerebellar
ataxia, Parkinson disease, Tourette syndrome, myoclonus, dystonia, reflex sympathetic
dystrophy (complex regional pain syndromes type 1), causalgia, complex regional pain
syndrome type 2, neurofibromatosis, chronic inflammatory demyelinating polyneuropathy,
Sjogren syndrome, lupus, interstitial cystitis, myasthenia gravis, hydrocephalus, nail patella
syndrome or residual limb pain, or treatment of these conditions.
Cannabinoid Augmentation Therapy/CAT
It is well-established that cannabinoids exert palliative effects on some cancer-associated
symptoms. In addition evidences obtained during the last fifteen years support that these
compounds can reduce tumor growth in animal models of cancer. Cannabinoids have been
shown to activate an ER-stress related pathway that leads to the stimulation of autophagymediated
cancer cell death. In addition, cannabinoids inhibit tumor angiogenesis and decrease
cancer cell migration. The mechanisms of resistance to cannabinoid anticancer action as well
as the possible strategies to develop cannabinoid-based combinational therapies to fight cancer
have also started to be explored.
Double-Edged Sword: Killing Cancer Cells can also Drive Tumor Growth
A team of researchers, including experts at BIDMC, has found that dead and dying cancer cells caused by chemotherapy and other targeted cancer therapies can, in turn, result in aggressive
tumor growth.“Conventional cancer therapy designed to kill tumor cells is
inherently a double-edged sword,” said senior author Dipak
Panigrahy, MD, scientist at the Cancer Center at BIDMC.
However, in a follow-up set of experiments, the researchers found a novel approach to preventing cancer resurgence by introducing a class of naturally occuring anti-inflammatories
called resolvins.
These resolvins may also be an effective component of treatment when added to existing chemotherapy.
Resolvins are autacoids of a specific lipid structure: dihydroxy or trihydroxy
metabolites of omega-3 fatty acids, primarily eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA) but also the docosapentaenoic acid
(DPA), clupanodonic acid. They are members of an expanding class of
polyunsaturated fatty acid (PUFA) metabolites termed specialized
proresolving mediators (SPMs). Other SPMs include the lipoxins, protectin
D1 and its related products, and the maresins. SPMs are locally formed
and locally acting cell signaling autacoids: they are made by cells and act
upon their parent or nearby cells to coordinate functional responses. SPMs
possess potent anti-inflammation, tissue protection, and tissue healing
activities in diverse animal models and accordingly are proposed to be
involved in resolving physiological inflammatory responses.
Their failure to form in adequate amounts is also proposed to underlie a broad range of
human diseases involving pathological inflammation. Metabolically stable
analogs of the SPMs, including the resolvins, are in development and being
tested in volunteers with chronic inflammation-related diseases.
The main treatment for cancer is by using chemotherapy and radiotherapy
which themselves are toxic to other viable cells of the body. Recently, there
are many studies focusing on the use of natural products for cancer
prevention and treatment. Of these natural products, honey also has been
extensively researched. The mechanism of the anti-cancer activity of honey
as chemopreventive and therapeutic agent has not been completely
understood.
The possible mechanisms are due to its apoptotic, antiproliferative, antitumor necrosis factor (anti-TNF), antioxidant, antiinflammatory, estrogenic and immunomodulatory activities.
Needless to say, Cannabinoids (CBD…) also are a natural source of Resolvin precursors and provide anti-inflammatory effects via multiple pathways, in excess to their antioxidant profile. Clinical study must ethically proceed given the public desire for, the expanding availability, and the limited toxicity arising from cannabinoid therapy.
Emphasis in any proposed endeavor must be noted toward grass root clinical data collection
and analysis, fit for review and community consideration/involvement.
The above information justifies the immediate initiation of combination/ integrative approaches toward urban cancer care protocols. Cannabinoid therapy is patient dependent and can be initiated prior to allopathic regimens, continued through standard therapies, and provided for post
therapy cancer prevention protocols.
Clinical Applications of Flotation/REST
The following reference results provide strong support for the hypothesis that Flotation/REST
serves as a powerful relaxation inducer and has clinical potential in working with patients who
have stress-related disorders. There have been several clinical studies that have employed
REST as a treatment.
The disorders treated include essential hypertension, muscle tension headache, anxiety disorders, chronic pain, psychophysiological insomnia, PMS, and rheumatoid arthritis (Fine and Turner, 1985; Rzewnicki, Alistair, Wallbaum, Steel,
Suedfeld, 1990; Fine and Tumer, 1985; Goldstein and Jessen, 1990; Turner, DeLeon, Gibson, &
Fine, 1993).
The treatment paradigms used in these studies were similar, with REST serving as
the primary method of relaxation induction and training.
All of these studies demonstrated
positive results from the use of REST. One of the unique effects of REST demonstrated in these
studies was that chronic pain patients frequently experienced an absence of all pain during
flotation, and that this spontaneous anesthesia could remain for up to several hours after
the session. Unfortunately, as with many bio-behavioral treatment approaches, the large scale
controlled trials have yet to be undertaken.
Flotation/REST and Performance Enhancement
A separate, exciting area is the use of Flotation/REST in the enhancement of human
performance. Several studies, carried out primarily in the research programs of Peter Suedfeld
at the University of British Columbia and Arreed Barabasz at Washington State University, have
demonstrated enhancement of scientific creativity, instrument flight performance, and
piano performance. Several studies of sports performance have had positive results
including studies of basketball, tennis, skiing, rifle marksmanship, and dart throwing. In
several of the studies the Flotation/REST condition was varied with relaxation, or imagery
training and always had a more powerful effect. Often, Flotation/REST was used with imagery or
without imagery, and no difference was, found. Flotation/REST, either wet or dry, was sufficiently
powerful to affect a change in performance. Barabasz suggests that because REST potentiates
imagery while disrupting over learned psychological processes, the technique is especially
suited not only for the acquisition of new im- proved skills but the unlearning of less adaptive
ones.
Flotation/Rest and Pain Management
An in depth examination of the role of Flotation/REST in the management of pain can provide us
with a clear picture of the psychophysiological nature of the treatment. Pain programs are
generally used as a last referral resort for patients whose intractable pain has not
responded to the traditional medical treatments. Bio-behaviorally based pain management
utilizes counseling and behavioral medicine techniques such as relaxation training, meditation.
biofeedback, guided imagery, and self-hypnosis.
The goals of such treatment are the development of pain avoidance skills, the establishment of routines for optimal fitness within the limitations of a disability, the reduction or elimination of pain, when possible, and/or the patients acceptance of some level of pain.
Flotation/REST can have an important role at several stages of the pain management
process. By reducing both muscle tension and pain in a relatively short time and without effort
on the part of the patient, flotation provides a dramatic demonstration of the benefits of
relaxation. Relief is immediate and, although temporary, offers promise of further relief
from REST and other relaxation-based strategies.
Symptom reduction gained from flotation can increase a patient’s motivation and interest in the remainder of the therapy plan. Pain patients generally come into treatment feeling suspicious and skeptical, requiring a clear demonstration that they can be helped. Flotation can be the vehicle for that demonstration.
The relaxation following flotation can be used to facilitate relaxation training. In the treatment
reported here, training in relaxation and other psychological pain control strategies
occurred during the flotation REST sessions as well as in counseling sessions. Specially
prepared audio programs introduced patients to breathing techniques, progressive muscle
relaxation, autogenic training, guided imagery and hypnotic suggestions for pain reduction while
they floated. Training and practice in those same techniques followed in counseling sessions
and at home.
The most common etiologies of pain in this group of patients were from motor vehicle
accidents, work accidents, or chronic illness. Most had endured their pain for longer than
six months and had also suffered various levels of anxiety, anger, and depression. These
emotional problems must be considered in the treatment of chronic pain patients. The first data
are pre-post pain ratings from 16 patients who floated from one to 16 flotation sessions. Each
patient reported on up to four body areas, providing a total of 253 pre-post , measures. The
average percentage of relief, as measured in decrease from the pre-session value, was 31.3%
for all sessions and all measures.
To determine whether flotation REST provides more pain relief to some parts of the body as opposed to others, these measurements were examined by body area. Pain reduction in most body areas was close to the overall mean of 31%, except the upper back, which showed a 63.6% pain reduction, the arms which showed a 48.2% reduction, and the legs, which showed a 15.3% pain reduction. The duration of relief varied from two hours to seven days.
A second set of data came from a survey mailed to patients who had completed the program.
The questionnaire asked patients to assess how much pain relief they received from the various
components of the pain program (Flotation, relaxation training, and counseling) and from other
treatments they had received medication (pills and shots), physical therapy, chiropractic, and
surgery. Short-term pain relief, long-term pain relief, relief from anxiety or stress, and relief from
depression were indicated separately. Additionally, they were asked whether each treatment
improved their outlook and/or helped them cope with their pain.
All 27 respondents had received treatments other than those from this pain program: 81% had
used pain medications; 56% had had some form of pain injections; 70% had received physical
therapy; 59% had received chiropractic treatment; 22% had undergone surgery. These patients
reported more short-term and long-term pain relief from flotation than from the other
therapeutic modalities.
For non-pain symptoms, the comparisons were even more striking. Patients reported far
more relief from anxiety and stress from flotation than any other modality. For depression,
flotation was equal to counseling at near 70%, with relaxation training at 53% and physical
therapy and medication at 20%. Patients also claimed to have reaped a variety of other benefits
from flotation, reporting improvements in sleep (65%), mental concentration (77%), energy
(46%), interpersonal relationships (54%), ability to work (35%), ability to cope with pain (88%),
ability to cope with stress (92%), and feelings of well-being (65%) resulting from flotation REST.
In answering the question, “Did this treatment improve your outlook toward your pain?”
96% responded positively for flotation, 100% for counseling, 100% for relaxation training,
50% for physical therapy, 24% for pain pills, 17% for pain shots, 15% for chiropractic. To
the question, “Did this treatment help you cope effectively with your pain?” 96%
responded positively for flotation, 92% for both relaxation training and counseling, 50% for
pain shots, 44% for pain injections, 38% for physical therapy, and 17% for chiropractic. It is clear
that flotation was rated on average as more effective than other treatments with respect to pain,
anxiety and depression relief.
Flotation/REST and Chronic Illness
Summing up thus far, the data are supportive of flotation/REST being useful in pain reduction,
stress and tension abatement, and mood enhancement. Besides chronic pain, other patients
treated at our facility were those with chronic physical illnesses, those with cancer, those
with trauma to the nervous system, those with depression or bipolar mood disorder.
anxiety disorders, and those suffering overwhelming stress.
Uniquely, Flotation/REST provides an effortless introduction to deep mental and physical
relaxation. The majority of our chronic illness patients suffered from autoimmune
diseases, including rheumatoid arthritis, lupus, scleroderma, and Reiter’s syndrome. For
these patients, discovering relaxation meant a dramatic reduction in symptoms, such as
joint pain, headache, fatigue and depression. Several patients with lupus reported that regular
flotation permitted them to reduce their dosage of prednisone while experiencing less
frequency and severity of symptoms.
Two patients with scleroderma reported relief from flotation. One reported relief from pain and stiffness that lasted almost a week after her third flotation session. As this patient continued she also experienced relief from her depression about the illness, a dramatic reduction in her use of steroids and other medications, a reduction in joint pain and swelling, and less frequent heartburn and
headaches.
After a three month course of treatment with flotation and counseling she was able
to return to her job.
Flotation/REST and Depression
When depression is in reaction to the circumstances of a physical injury or illness, Flotation /
REST can produce an immediate elevation in mood, probably due to the mood enhancing
effects of deep relaxation as well as the optimism that occurs with the experience of
physical relief.
When depression is the primary diagnosis, flotation is best used as an adjunct to counseling and then only after the patient has gained a modicum of feeling in control. Caution is necessary in administering REST with depressed patients due to the often obsessive nature of negative thinking that will continue during the REST session.
Once these patients have developed a better understanding of their disorder, flotation REST can be a mood elevator that speeds the course of therapy, especially when combined with positive guided imagery during the sessions.
REST and Applied Psychophysiology
The REST environment can be viewed, from a biofeedback perspective, as a system that
enhances the connection between consciousness and physiology by reducing external
information rather than amplifying internal information. We describe biofeedback as a process of
amplifying and displaying information about processes that we normally do not attend to or are
unable to discriminate from the wealth of informational noise always present.
REST reduces environmental noise, and in a flotation environment one is able to be aware of all sorts of physiological information, (i.e. muscle tension, heart rate, etc.) that we are often not aware of in
normal quiet environments.
REST is an ideal environment for the acquisition of biofeedback based learning. Many
years ago Lloyd and Shurley published a paper demonstrating its effect on the acquisition of
single motor unit control. Acquisition of single motor unit control was superior in the REST
chamber (Lloyd & Shurley, 1976). Our investigations found the same advantage with heart rate
control. Similarly Dry-REST environments might be exceptional environments for neurofeedback
training. While we have learned much about REST in the last twenty years, its potential in
applied psychophysiology has barely been exploited. In this age of cyberspeak, we might begin
to think of expanding the clinical bandwidth of applied psychophysiology by taking another look
at REST.