Harm Reduction Journal 2012, 9:1 doi:10.1186/1477-7517-9-1

Mark Collen
PainExhibit.com, 9008 El Cajon Way, #4, Sacramento, CA, 95826, USA
Email: Mark@PainExhibit.com

Abstract
Neuropathic pain affects between 5% and 10% of the US population and can be refractory
to treatment. Opioids may be recommended as a second-line pharmacotherapy but have
risks including overdose and death. Cannabis has been shown to be effective for treating
nerve pain without the risk of fatal poisoning. The author suggests that physicians who
treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and
prescribe it when appropriate prior to using opioids. This harm reduction strategy may
reduce the morbidity and mortality rates associated with prescription pain medications.

Keywords: cannabis, cannabinoids, opioids, neuropathic pain, chronic pain, harm
reduction, ethics

Neuropathic pain (NP) is defined as pain caused by a lesion or disease of the central or
peripheral somatosensory nervous system.[1] NP affects between 5% and 10% of the US
population [2] and examples include diabetic neuropathy, complex regional pain syndrome,
radiculopathy, phantom limb pain, HIV sensory neuropathy, multiple sclerosis-related pain,
and poststroke pain.[3] Neuropathic pain is difficult to treat and opioid analgesics are often
prescribed.[4] Recent science has demonstrated efficacy in treating NP with cannabis,[5,
6, 7] a safer drug than opioids.[8] This paper suggests that physicians who treat
neuropathic pain should prescribe cannabis prior to using opioids as a harm reduction
(HR) strategy. Topics covered include how harm reduction applies to prescription opioid
substitution, the legality of medicinal cannabis, a comparison of cannabis to opioids, the
science on treating NP with cannabis and cannabinoids, and the ethics of prescribing a
drug which is deemed illegal on the federal but not the state level.
Medicine relies upon the principle of, “First, do no harm,” and one might supplement the
axiom to read – “First, do no harm, and second, reduce all the harm you can.” “Harm
reduction” or “harm minimization” can be defined in the broadest sense as strategies
designed to reduce risk or harm.[9] Those harmed may include the individual, others
impacted by the harmed person, and society.[9] The substitution of a safer drug for one
that is more dangerous is considered harm reduction.[10] Specific examples of HR include
prescribing methadone or buprenorphine to replace heroin,[11] prescribing nicotine
patches to be used instead of smoking tobacco,[12] and prescribing intranasal naloxone to
patients on opioid therapy to be utilized in case of overdose.[13] Substituting cannabis for
prescribed opioids may be considered a harm reduction strategy.
Under the Federal Controlled Substance Act “marihuana” is illegal and classified as a
schedule I substance – meaning it has a high potential for abuse and no accepted medical
use.[14 ] However, sixteen states and the District of Columbia have legalized cannabis for
medicinal use and these include Alaska, Arizona, California, Colorado, Delaware, Hawaii,
Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island,
Vermont, and Washington.[15] Each state law differs but all allow physicians to “authorize”
or “recommend” cannabis for specific ailments.[16] This “recommendation” affords legal
protections for patients to obtain and use medicinal cannabis, and may be considered the
“prescription.”
Cannabis (Cannabis sativa) and the opium poppy (Papaver somniferum) are both ancient
plants that have been used medicinally for thousands of years.[17, 18] The natural and
synthetic derivatives of opium, including morphine, are called “opioids.”[19]
“Cannabinoids” is the term for a class of compounds within cannabis of which delta-9-
tetrahydrocannabinol (THC) is the most familiar.[20] Besides THC, approximately 100
other cannabinoids have been identified [21, 22] including one of special scientific interest
called “cannabidiol” (CBD).[23] The human body produces both endogenous
cannabinoids (endocannabinoids) and opioids (endorphins) and contains specific
receptors for these substances.[24, 25] There is an extensive literature on opioids but far
less on cannabis/cannabinoids (CC).
Adverse effects from opioids include respiratory depression, sedation, sleep disturbance,
cognitive and psychomotor impairment, delirium, hallucinations, seizures, hyperalgesia,
constipation, nausea, and vomiting.[26-28] Adverse events from cannabis/cannabinoids

include psychotic episodes, anxiety or panic reactions, memory impairment, reduced
concentration, disorientation, lowered blood pressure and increased heart rate.[7, 29, 30,
31] In a systematic review Wang and colleagues found most adverse events for short term
cannabis use were not serious, and there was a lack of evidence to determine
adverse effects for long-term use.[32] Opioids and cannabis share issues of addiction,
physical dependence, tolerance and withdrawal.[5, 33, 34]
Between 1999 and 2006 approximately 65,000 people died from opioid analgesic
overdose.[35] Regarding fatal overdose from cannabis, Carter and colleagues write, “…
this well documented fact: no one has ever died from an overdose of cannabis.”[8] In
addition, there is insufficient data to demonstrate smoking cannabis causes lung cancer
[36] but long-term use is associated with an increased risk of respiratory problems.[37]
Although, eating cannabis [38] avoids the respiratory issues. In 2001 the total cost of
prescription opioid abuse was estimated at $8.6 billion.[39] Unfortunately, there are no
comprehensive studies on the total cost of cannabis abuse. However, enforcing the
prohibition on cannabis costs an estimated $7.7 billion per year.[40] Since the federal and
most state governments view any use of cannabis as abuse – including medicinal use –
one might include this cost. According to a report from the Substance Abuse and Mental
Health Services Administration between 1999 and 2009 admissions for treatment of
nonheroin opioid abuse increased approximately 516% while admissions for cannabis saw
a 53% rise.[41]
Nerve pain can be refractory to treatment [42] and opioids are often used as a second-line
therapy while antidepressants and anticonvulsants are commonly used first.[4, 43]
Moreover, opioids may provide only limited pain relief and as Henry McQuay writes, “…you
may be able to decrease neuropathic pain with strong opioids, but the decrease is often
slight and is achieved with an adverse effect burden that will not be tolerable over weeks
to months.”[44] Cannabis and cannabinoid research is in its relative infancy and many
studies are of short duration and with small sample sizes.[6] However, a number of review
articles suggest that treating neuropathic pain with cannabis/cannabinoids is efficacious
and with moderate adverse effects.[5-7] The most thorough of the systematic reviews was
of randomized controlled trials (RCTs) of CC therapy [6] which looked at nine studies [45-
53] whose focus was on treating different types of neuropathic pain with either smoked
cannabis,[45-48] a synthetic cannabinoid similar to THC,[49, 50] or a whole plant extract of
THC and CBD in a 1:1 ratio.[51-53] CBD may moderate the psychoactive effect of THC
and have analgesic properties.[24] Seven of the nine studies demonstrated efficacy for
using CC for neuropathic pain [45-49, 52, 53] while two had mixed results,[50, 51] and
eight of the nine studies found no serious adverse events.[45-51, 53]
A closer look at the four RCTs which evaluated smoked cannabis for neuropathic pain [45-
48] reveals some common and contrasting elements (Table 1). Two of the studies, Ware
et al. [45] and Wilsey et al., [47] examined cannabis in treating a variety of NP conditions;
while the other two, Ellis et al. [46] and Abrams et al., [48] explored the effects of cannabis
on HIV-related neuropathic pain. Both Wilsey et al. [47] and Abrams et al.[48] required
participants to have previously used cannabis in order to reduce the risk of adverse
reactions from psychoactive effects. The RCTs used cannabis with a variety of THC
strengths ranging from 0% for placebo [45-48] to 9.4% in Ware et al.[45] Each study required participants to continue taking their regular medications during the cannabis trials
and all found a significant decrease in pain compared to placebo.[45-48] In addition,
adverse events were tolerable for the vast majority of participants.[45-48]
Commentators have suggested that patients should use whole plant cannabis, as opposed
to chemical derivatives, because of other potentially beneficial compounds.[8, 19] In
addition, a number of articles have reported on interactions between cannabinoid and
opioid receptors which may result in enhanced analgesia and a synergistic effect when CC
is added to opioids.[54, 55] This may translate into patients being able to reduce their
opioid intake with adjuvant cannabinoid therapy.[5,29]
Although prescribing cannabis is legal in 16 states and the District of Columbia, it remains
illegal at the federal level. Portions of the American Medical Association’s Code of Medical
Ethics, Opinion 1.02 – The Relation of Law and Ethics reads, “Ethical values and legal
principles are usually closely related, but ethical obligations typically exceed legal duties.
In some cases, the law mandates unethical conduct.” “In exceptional circumstances of
unjust laws, ethical responsibilities should supersede legal obligations.”[56] An
“exceptional circumstance of unjust laws” may be interpreted as the federal ban on
cannabis for medical use. Sixteen states and the District of Columbia found the federal
government’s prohibition on prescribing and using medicinal cannabis so unjust as to
create laws in direct violation of federal statute. Therefore, one could surmise that
prescribing cannabis for the purpose of harm reduction is ethical even though it violates
federal law. In addition, Hayry suggests that the idea of “freedom” also provides an ethical
reason for prescribing cannabis and he writes, “… whatever the legal situation, respect for
the freedom of the individual would imply that requests like this (for medicinal cannabis)
should be granted, either by health professionals, or by society as a whole.”[57]
In states where medicinal cannabis is legal, physicians who treat neuropathic pain with
opioids should evaluate their patients for a trial of cannabis and prescribe it when
appropriate prior to using opioids. There is sufficient evidence of safety and efficacy for
the use of CC in the treatment of nerve pain relative to opioids and as Carter et al write,
“From a pharmacological prospective, cannabinoids are considerably safer than
opioids…”[8] Prescribing cannabis in place of opioids for neuropathic pain may reduce the
morbidity and mortality rates associated with prescription pain medications and may be an
effective harm reduction strategy.
[The subject of cannabis dosing is beyond the scope of this paper but those interested
should consider reading Carter GT, Weydt P, Kyashna-Tocha M, Abrams DI. Medicinal
cannabis: rational guidelines for dosing. IDrugs 2004;7:464-70.]

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