Cannabis Enables Pain Patients to Cut Opiate Use;

“It wasn’t just marijuana that got prohibited, it was the truth about history.” 95 —Tod Mikuriya, MD 8 O’Shaughnessy’s The Journal of Cannabis in Clinical Practice Autumn 2018

Logical response to a public health emergency— Cannabis enables pain patients to cut opiate use; Availability would reduce ER visits and OD deaths By Dustin Sulak, DO Despite the widespread prescribing of In the late 1990s, Purdue Pharmaceu- opioids for chronic pain, the evidence that ticals aggressively marketed OxyCo- opioids actually help with this condition is done, advising physicians that their new surprisingly weak. A review in the Annals semi-synthetic opioid was less addicting of Internal Medicine in 2015 summarized, than true opiates such as codeine. Similar “Evidence is insufficient to determine the claims were made by other opioid manu- effectiveness of long-term opioid therapy facturers, including Johnson & Johnson/ for improving chronic pain in function.” Janssen, Glaxo, and Abbott Laboratories. The authors analyzed 34 studies on adults Between 1999 and 2010, the sales of pre- with chronic pain who had been using opi- scription opioids quadrupled —and so did oids for more than three months. They were the rate of opioid overdose deaths. unable to find a single study that assessed Enough opioids were prescribed in 2010 outcomes longer than one year of use re- to give a one-month supply of five milli- lated to pain, function, or quality of life! grams of hydrocodone (Vicodin, a semi- They did, however, find increased risk synthetic made by Abbot) every four hours of serious harm associated with long-term to every adult in the U.S. opioid use: overdose, abuse, fractures, heart attacks, and sexual dysfunction. And The epidemic that began large- a high number of people using prescription opioids end up abusing heroin. ly in the doctor’s office could not Finally recognizing this gap in the sci- Papaver somniferum (“the sleep-inducing Poppies grown for medical use in Tasmania be contained there. entific literature, a study published in the poppy” in poster at left) produces opium in by international agreement are bred so that Journal of the American Medical Associa- its seed pod. The milky opium may consist of thebaine, not morphine, is the dominant opi- four to 20 percent morphine and other pain- oid. A Johnson & Johnson subsidiary, Tas- By 2010, one in 20 Americans over the tion compared long-term opioid with non- reducing alkaloids. Semisynthetic opioids manian Alkaloids, was producing about half age of 12 had used an opioid medication opioid treatment (such as NSAIDs, anti- contain small amounts of natural alkaloids. the world’s legal supply as of 2016. non-medically, or used it other than as pre- depressants, neuroleptics) in 265 patients scribed. The epidemic that began largely with chronic pain. Researchers found no common in the opioid group. effective treatments, most doctors turn to in the doctor’s office could not be con- significant difference in pain-related func- The doctors’ dilemma opioid medications because they’re out of tained there. tion over 12 months, but the pain intensity We clinicians see people coming in with alternatives —or so they think. Heroin as a cause of opioid overdose was significantly reduced in the non-opioid chronic pain, and we feel obligated to do Thankfully, there is an alternative, an op- began rising sharply in 2011. Nearly 80 group. As expected, adverse medication- something to help them. After patients fail tion that has been proven safe and effective percent of heroin users reported using pre- related symptoms were significantly more respond to more conservative and often in- in the treatment of chronic pain: cannabis. scription opioids before initiating heroin continued on page 34 use. The number of deaths involving fentan- Even in ‘progressive’ California yl, a synthetic opioid, rose from 3,000 in 2013 to 20,000 in 2016. In 2016 some 64,000 Americans died of Medical Boards’ Restrictive Practice Guidelines drug overdose deaths —more than died during all the years of the Vietnam War. Challenged by Society of Cannabis Clinicians In 2017 the number had risen to 72,000 — By Fred Gardner higher than deaths from car crashes. they authorize to use cannabis, the percent- “The use of medicinal canna- Physicians in the United States are li- US Americans account for five percent age of approvals issued to patients under censed by state medical boards. Licenses bis is not prima facie evidence of of the world’s population and consume age 30, and the number of plants they au- can be suspended or revoked when a board impairment or abuse.” 80 percent of the world’s opioids. We’re thorize patients to grow. deems physicians guilty of serious infrac- using opioids to such an extent that some The FSMB also sought to prevent clini- —Stephen Robinson, MD tions. countries have trouble accessing opioids cians who approve use by patients from us- Typically, members of a state medical article entitled “Medical Board Expecta- for essential needs like post-surgical or ing cannabis as medicine themselves. board have been appointed to a two-year tions for Physicians Recommending Mari- end-of-life treatment. Even US hospitals At the FSMB convention in San Diego term by the governor. (Many have contrib- juana” in the prestigious Journal of the are now reporting shortages of morphine in April 2016, delegates from all 50 states uted money to the governor’s party.) They and 20 US Territories agreed unanimously American Medical Association (JAMA). and hydromorphine. meet quarterly and vote on policy matters. Their “viewpoint” essay ran online June 16 According to a 2014 report by Express that their medical boards should take steps The board’s business is conducted by ca- to adopt the federation’s guidelines. Vot- and in the print edition August 9. Scripts, 50 percent of people who took reer bureaucrats and gun-carrying “peace ing “aye” for the California board were The Society of Cannabis Clinicians prescription opioids for more than 30 days officers” who investigate complaints Executive Director Kimberly Kirchmeyer (SCC, a doctors’ group founded in 2000 in their first year of use continued to use against physicians. We, the people, count and Howard Krauss, MD, a Los Angeles by Tod Mikuriya, MD) urged the Medical opioids for three years or longer. Half of on them to identify and expel quacks, sex- opthalmologist who has never approved Board of California (MBC) to reject the them were being prescribed short-acting ual predators, incompetents and profiteers cannabis use by a patient. federation’s approach. opioids such as Vicodin, which are most —important, meaningful work. FSMB president Humayun Chaudhry, At a July 2016 meeting of the Califor- likely to lead to addiction and abuse. Near- Some infractions by physicians are gross DO and two co-authors then published an continued on page 16 ly 60 percent of the patients were taking and readily provable. Others are subtle opioids in combination with drugs that are and subject to interpretation, such as “fail- known to make opioids more dangerous ure to conduct a good-faith examination.” and an overdose more likely. Physicians who approve cannabis use by

Dustin Sulak, DO, patients have frequently been the target of is a practitioner and medical board investigations in California advocate of integra- and other states. tive medicine, which Being investigated is a costly, time-con- combines conven- suming process that involves hiring a law- tional and alternative yer. Zealous undercover investigators can approaches to health- frame physicians by feigning symtpoms. care. He directs the In 2015 an obscure but powerful bureau- Integr8 Health Clinics cratic entity called the Federation of State in Maine and Massachusetts. Medical Boards (FSMB) took aim at Can- Sulak has helped more than 18,000 patients use cannabis as medicine. He educates nabis Approving Doctors (CADs). patients and fellow clinicians via the Healer. The FSMB, a non-profit that employs 80 com website and frequent conference presen- people in Eulis, Texas, and six lobbyists Stephen Robinson, MD, representing the Society of Cannabis Clinicians at a meeting of the tations. This article is based on talks given in Washington, D.C., developed “model Medical Board of California, warned that proposed “model guidelines” would lead to special- in response to the US opioid epidemic. (New guidelines” that would trigger investiga- ists being targeted by the board’s Enforcement Division and pressured to not use cannabis as England is one of the regions hardest hit.) tions of CADs based on how many patients medicine themselves. At right, board members Katherine Feinstein and Michael Bishop, MD. —34— O’Shaughnessy’s • Autumn 2018

Cannabis/Opioids from page 1 But most doctors don’t know about that Cannabinoid-opioid pharmaceutical In 2017 an Australian group led by Su- option. They find themselves face-to-face zanne Nielsen published a meta-analysis with patients who say, “My pain is worse. of animal studies that examined the effects The opioids aren’t working, I need more. of cannabinoid-opioid co-administration. If I don’t get them I’m not going to be able Seventeen of 19 studies demonstrated what to go to work, I’m not going to be able to Nielsen calls an “opioid-sparing effect.” support my family, I’m not going to be able When combined with THC, the effective to function...” It’s hard for clinicians to say dose of morphine was 3.6 times lower and ‘no,’ because they don’t have another tool. the effective dose of codeine 9.5 times lower. But does this translate to the human Cannabis can prevent opioid experience? In a 2011 study, Donald Abrams, MD, tolerance-building and the need Manufactured by Parke, Davis, Chlor-Anodyne was one of the most popular compound drugs of the 19th century, It combined morphine, added a low dose of vaporized cannabis to for dose escalation. Cannabis cannabis, and capsicum, taking advantage of the interplay among the regimen of 21 patients who were using can treat the symptoms of opioid our three receptor systems that control pain (endorphin, endocan- high-dose opioids (ineffectively) to treat withdrawal. And cannabis is saf- nabinoid, and vanilloid), and likely providing better outpatient pain chronic pain in a hospital setting. The can- relief than anything available in the pharmacy today. nabis, provided by the National Institute on er than other harm-reduction op- Drug Abuse, contained 3.56 percent THC tions for people who are addicted —very low potency, given what’s available Pain medicines that combine cannabi- to or dependent on opioids. port that currently available cannabinoids to US consumers. are safe, modestly effective analgesics that noids and opioids to take advantage of Patients vaporizing three times daily re- these overlapping receptor system are, in My goal is to carry the message that there provide a reasonable therapeutic option ported a significant decrease in pain —27 fact, nothing new. One of the most popu- is another tool. Cannabis can replace and in the management of chronic non-cancer percent. Perhaps more potent cannabis and/ lar compound drugs of the 19th century, reduce the dose of opioid medications pain.” or a different delivery method would have Chlor-Anodyne combined morphine, can- needed to control pain. Cannabis can pre- led to even greater relief. Several subse- nabis, and capsicum, taking advantage vent opioid tolerance-building and the need Seventeen of 10 animal studies quent studies have also demonstrated sig- of the interplay among our three receptor for dose escalation. Cannabis can treat the had what Nielsen called an “opi- nificant pain relief from adding cannabis in systems that control pain (endorphin, en- symptoms of opioid withdrawal. And can- patients with chronic pain that is refractory oid-sparing effect.” docannabinoid, and vanilloid), and likely nabis is safer than other harm-reduction to opioid drugs. providing better outpatient pain relief than options for people who are addicted to or A 2018 study from Ziva Cooper, PhD, Cannabinoid-Opioid Synergy anything available in the pharmacy today, dependent on opioids. examined the pain-relieving effects of Cannabinoids and opioids have a few Researchers using rodent models of Randomized, placebo-controlled trials various combinations of cannabis (pla- things in common. Both are derived from pain have been demonstrating since the —RCTs, considered the gold-standard by cebo or 5.6% THC delivered via a joint) plants with thousands of years of histori- late 1990s that administering opioids and medical scientists—show that cannabis and oxycodone (placebo, 2.5 mg, and 5 mg cal medical use. Both mimic substances cannabinoids together results in a greater- can be used to treat chronic pain. capsules) on healthy volunteers using the our bodies produce: endocannabinoids and than-additive anti-pain effect. A team at the In contrast to the Annals of Internal “cold pressor test.” (Subjects submerged endorphins. And both change the way we Medical College of Virginia determined Medicine article that found no evidence their hand in ice water, rating the time until experience pain. Is there a basis for using that a dose of 20 milligrams-per-kilogram- supporting the use of long-term opioids, a the onset of pain, the time until they could these two classes of medication together? of-body-weight of either morphine or THC June 2015 review article by Mary Lynch no longer tolerate the pain, and the inten- Opioid and cannabinoid receptors are achieved 30 percent of the maximum pos- and Mark Ware in the Journal of Neuroim- sity of the pain.) Cooper also evaluated present in pain areas of the brain. (Recep- sible pain-reducing effect. But the two mune Pharmacology evaluated 11 random- whether cannabis increased the degree to tors can be thought of as antennae or little drugs given together resulted in maximum ized clinical trials published in 2010-2014. which subjects liked the oxycodone and keyholes. When an opioid or cannabinoid pain reduction (100%). This demonstrated “The quality of the trials was excellent,” wanted to take it again. fits into its receptor, it has some effect on a synergy between opioids and canna- they wrote. “Seven of the trials demon- Cooper’s findings confirm the extensive the cell, changing its physiology.) binoids, since 30 plus 30 equaled 100 in strated a significant analgesic effect. preclinical literature: administered alone, Both opioid and cannabinoid receptors terms of pain relief. Using morphine alone, “Several trials also demonstrated im- only the 5 mg dose of oxycodone increased are also present in areas that influence 100mg/kg dose was required for maximum provement in secondary outcomes (e.g., pain threshold and tolerance compared to addiction and reward-seeking behavior. relief. sleep, muscle stiffness and spasticity). Not only are the two receptor types co- continued on next page Adverse effects most frequently reported, localized in these nerve cells, they’ve been such as fatigue and dizziness, were mild show to interact with each other, seemingly to moderate in severity and generally well working together in the great symphony of tolerated. This review adds further sup- our human physiology.

Deaths from presciption-opioid overdoses in US by age, 1999-2016. Vertical scale shows deaths per 100,000 population. The sharpest rise in recent years has been in the 25-to-34 and 35-42 age groups. Source: NCHS, National Vital Statistics System, Mortality

Opiod overdoses as a cause of death between 2000 and 2016 rose from five per 100,000 Americans abpve age 12 to more than 13 per 100,000. In 2011 prescription opioids (natural and semi-synthetic) were responsible for more than twice as many deaths as heroin and fentanyl combined. By 2015 heroin and fentanyl each exeeded prescription opioids as the cause of OD fatalities. In 2011 prescription opioids (natural and semi-synthetic) were responsible for more than twice as many deaths as heroin and illicit fentanyl combined. By 2015 heroin and fentanyl each exeeded prescription opioids as the cause of OD fatalities. Semisynthetic opioids contain small amounts of the natural alkaloids made by the poppy plant. Hydrocodone contains codeine. Oxycodone contains thebaine. Hydro- morphone contains morphine. Synthetics—Fentanyl, Demerol, Dilaudid, Norco, Lortab, Atarax, Methadone, Buprenorphine— are designed in the laboratory by chemists who look to the mo- lecular structure of natural alkaloids for inspiration. “Opiate” is a term reserved for compounds produced by the plant, such as morphine, codeine, thebaine, and papaverine. (Just as Cannabis plants make numerous chemically distinct cannabinoid acids, Papaver somniferum plants make numerous, distinct opium alkaloids.) Deaths from presciption-opioid overdoses by state in 2015-2016. Overdose deaths Opioids cause death by suppressing the central nervous system, which is respon- caused by prescription drugs continued to rise in some states (red). Orange indi- cates states with prescription-opioid death rates near the national average. O’Shaughnessy’s • Autumn 2018 —35—

Cannabis/Opioids from previous page placebo – 2.5 mg of oxycodone did not many lives could be saved with a program change these measures. and education? We can’t wait around for When combined with active cannabis, this, it has to happen now. however, the 2.5 mg dose of oxycodone did increase the pain threshold and tolerance compared to placebo and active cannabis alone. In other words, adding cannabis made an ineffective dose of oxycodone into an effective dose. Furthermore, adding cannabis to the 2.5 Colorado’s legalization of recreational mg oxycodone dose increased the degree cannabis sales and use in 2014 led to a to which subjects liked the capsule and 0.7% decrease in opioid-related deaths per wanted to take it again. Cooper notes that month, according to a paper in the Ameri- adding cannabis to oxycodone not only po- can Journal of Public Health. A graph of tentiates the analgesia, it may also increase Association between medical and adult-use marijuana laws on Medicaid-covered opioid opiod deaths per month between 2000 and its efficacy as a harm reduction strategy— prescribing rate were graphed by Wen and Hockenberry. Schedule 2 opioids include Oxyco- 2015 shows the trend beginning to reverse. and its abuse liability. done, hydrocodone, fentanyl, morphine, and codeine. Schedule 3 narcotics include: combination products containing less than 15 milligrams of hydrocodone per dosage unit (Vico- While cannabis amplifies the anal- din), products containing not more than 90 milligrams of codeine per dosage unit (Tylenol gesic effect of opiods, it in no way with codeine), and buprenorphine (Suboxone). amplifies their dangerous effects. activity level, and concentration. I don’t make a sharp distinction between Treating Chronic Pain A paper by Wen and Hockenberry in “adult use” and “medical use.” A study in A study conducted in Israel by Simon JAMA Internal Medicine April 2 looked at Colorado of people buying cannabis for Haroutounian and colleagues at Hadassah- pain drugs and opioid prescribing between “recreational use” found many were us- Hebrew University Medical Center, pub- 2011 and 2016. Eight states implemented ing it for help getting to sleep. There’s a lished in 2016, looked at 176 patients with medical cannabis programs during that continuum. People defining their use as Imagine if we had rescheduling and fed- chronic pain, 73 of whom were on opioids time frame: Connecticult, Delaware, Il- recreational may be enhancing their qual- eral legalization! How many fewer people at baseline. They were all given 20 grams linois, Maryland, Massachusetts, Minne- ity of life and less likely to use other drugs, would be dying every day? of cannabis per month and a choice of how sota, New Hampshire, and New York. Four which is a medical result. Safety and Efficacy to ingest it: smoked, in cookies, or in an states legalized adult use: Alaska, Colora- I completely agree with the authors’ con- While cannabis amplifies the analgesic olive oil extract. do, Oregon, and Washington. clusion: “Marijuana liberalization alone effect of opioids, it does not amplify their Patients were encouraged to decrease their Just by having medical cannabis laws, cannot solve the opioid epidemic. It is but most dangerous effects. Opioids stimulate other medications for treating pain if they states achieved a six percent decrease in one potential aspect of a comprehensive receptors in the cardio-respiratory centers could. They were given titration instructions opioid prescriptions! Adult use marijuana package to tackle the epidemic.” —the part of the brainstem that controls — basically “start low, gradually increase laws were associated with a 9.78% de- heart rate and breathing. Too many opioids dosage, use it three times daily.” And by crease. will shut down these essential functions. the seven-month mark, 44 percent of those Since there are virtually no cannabinoid who were on opioids at baseline had com- receptors present in those areas, cannabis pletely discontinued their opioid therapy. The same issue of JAMA Internal Medi- does not share these potentially lethal side Also in 2016, a survey of 244 pain pa- cine contained an article by Ashley Brad- effects. By adding cannabinoids to opi- tients by Kevin Boehnke and colleagues at ford and University of Georgia co-authors Given more than 67 million Medicaid oids in the treatment of pain, we produce University of Michigan’s School of Public (including her father) looking at Medicare participants, the potential savings to the a greater therapeutic index: the lethal dose Health found that medical cannabis use Part D prescribing associated with state- federal government are enormous. of the opioid treatment stays the same, but was associated with an overall 64 percent level medical cananbis laws. They found Note that the researchers were tabulat- the effective dose goes way down. So it’s decrease in opioid use, a decrease in the a 14.4 percent reduction in states that al- ing the number of opioid prescriptions for actually safer for patients to use the combi- number and severity of side effects from lowed dispensaries and a 6.9 percent re- which Medicaid reimbursed —not mor- nation than opioids alone. other medications, and a 45% improve- duction in states that only allowed home phine equivalents. ��Number of prescrip- One of the biggest problems with long- ment on a scale assessing quality of life. cultivation. tions tells more about opioid cessation than term opioid treatment is that it stops work- In a 2017 cohort study from Jacob Vigil Bradford et al documented significant de- it does about reduction of use. ing. People build up tolerance to opioids. and colleagues at the University of New creases in hydrocodone and morphine pre- In the clinic, If I’m prescribing someone They come back every three to six months Mexico, 37 habitual opioid-using, chronic scriptions. They were looking at prescrip- 80 milligrams of morphine three times a saying, “I want more, I need more.” pain patients enrolled in New Mexico’s tions by drug name and did not convert day, and I get him down to 10 milligrams I saw this in my medical training, es- medical cannabis program were compared the doses into morphine equivalents. So, of morphine three times a day, that’s a huge pecially during residency. It was the bane to 29 non-enrolled patients. In the medical again, we’re not looking at dosage-reduc- improvement. But he’s filling the same of the primary-care provider’s existence. cannabis group, 84 percent of patients (31) tion data, which would reveal a lot. People number of prescriptions. What to do about these patients for whom- reduced their opioid dose and 41 percent are decreasing their dose —that’s what I’m we don’t have a better solution? (15) ceased using the drugs. seeing in the clinic. Every once in a while I would see a In the non-cannabis group, 45 percent People are decreasing their Bear in mind that medical cannabis laws patient who came in on a stable dose of (13) reduced their opioid dose and only one dose —that’s what I’m seeing in are associated with people getting off opi- opioids —for example five milligrams of patient ceased using opioids. There was a oids even with no specific program helping the clinic. oxycodone three times a day— and never clear trend of opioid dose reduction in the them do so. The states offer no education, asked for a dosage increase. I started to cannabis group and opioid dose escalation So a reduction in number of prescriptions no encouragement to use cannabis to re- wonder, ‘Why are these patients so differ- in the non-cannabis group. The medical is not showing the taper, it’s showing dis- duce opioid use. In most states with medi- ent from all the other patients that are tak- cannabis group also experienced marked continuation. That’s a great ultimate goal, cal marijuana laws, Opioid Use Disorder is ing opioids?’ And I started to ask them di- improvements in quality of life, social life, but not always what we can do. not even a qualifying condition There are more than 115 people dying of rectly and was surprised to learn that these opioid overdose in the US every day. How patients had a clear understanding of their strategy to prevent opioid tolerance and dose escalation. I was told, “This is what I’m doing, Doc. I’m using cannabis in combination with the pills and it makes them more powerful, it makes it so I don’t need more.” I re- member one patient in partic- ular that pulled his cannabis out of his pocket and insisted that I smell the answer to my question. When I looked at the primary literature, I found that my patient’s strategy had a valid scientific basis. Diana Cichewicz and colleagues reported that animals treated with combination THC and Daily doses presecribed for opioids through Medicare Part morphine avoid tolerance to In study by Vigil et al, mean prescribed daily opioid dose declined over the course of 18 D went down after states passed medical cannabis laws. the opioid, maintain anal- months among chronic pain patients enrolled in New Mexico’s Medical Cannabis Program Bradford et al reported a 14.4% reduction in states that al- gesic efficacy, and actually (blue). Daily opioid dose rose among patients in a comparison group (orange). Vertical scale lowed dispensaries (top half of table) and a 6.9% reduction shows mean daily dose in morphine equivalents. Lines show the trends. in states that only allowed home cultivation (bottom half). continued on next page —36— O’Shaughnessy’s • Autumn 2018

Cannabis/Opioids from previous page have increased numbers of opioid recep- third of opioid overdose deaths in 2009, ac- States with the most restrictions take, improve the pain relief that opioids tors in the spinal cord. cording to the CDC. on patients’ acccess to cannabis provide, prevent opioid dose escalation This is the opposite of what happens While Suboxone is safer than methadone, and tolerance —it can also treat the symp- when they’re treated with morphine alone. it can still cause a fatal overdose, especial- achieved the least reduction in toms of opioid withdrawal: nausea, vomit- The dose of THC needed to preserve the ly if taken with other drugs that suppress opioid-related mortality. ing, diarrhea, abdominal cramping, muscle effectiveness of morphine was so low that cardio-respiratory function, such as a ben- spasms, anxiety, agitation, restlessness, it produced no significant analgesia on its zodiazepines, which are often prescribed states with the most restrictions on pa- insomnia, runny nose and sweating – all own. to treat anxiety and sleep disturbance right tients’ acccess to cannabis achieved the symptoms that cannabis is well-known to Harm Reduction alongside the Suboxone. least reduction in opioid-related mortality. ameliorate. While we would like to imagine that ev- Other studies have shown that medical Cannabinoids have repeatedly been eryone with addiction problems can suc- Cannabis has a lower risk of and adult use cannabis laws are associated shown to promote neuroplastic changes in cessfully avoid all potentially addicting with less opioid prescribing/dispensing, the brain —structural alterations related to substances, the medical community has dependence than any other psy- fewer opioid-related emergency room vis- new patterns of thought, perception, and finally recognized that that’s not practi- choactive substance. its, and significant cost savings for states behavior. In animal models of anxiety, psy- cal. While the path of abstinence is effec- and the federal governement. chosis, depression, and memory impair- tive for certain individuals, it just does not How does cannabis compare to metha- In 2016 the U.S. Centers for Disease ment, cannabinoid-induced neurogenesis work for everyone. done and Suboxone as a potential harm Control released new guidelines for pre- is associated with behavioral improve-

reduction agent? scribing opioids to patients with chronic ment. These are precisely the types of Mainstream medicine employs It has a lower risk of dependence than pain. Their goal was to restrain clinicians’ changes needed to get someone out of the any other psychoactive substance. Most cycle of addiction and into a new phase in two opioid drugs as harm-reduc- irresponsible prescribing practices and tar- people who stop using cannabis are able to get the source of the opioid problem. Per- their life. Perhaps this is another reason tion alternatives in treating opi- do so without any formal treatment. And haps, in a small acknowledgment of the why some cannabis users are more likely oid dependence: Methadone and cannabis has a low risk for abuse and di- potential of cannabis to help with the opi- to find success in treatment for Opioid Use Disorder. Buprenorphine version, especially in non-smoked forms oid problem, the section on urine drug test- such as tinctures and sprays. The slower ing stated: “Clinicians should not test for onset makes the cannabis less rewarding Pain worsens depression and anxiety Instead of insisting on abstinence, we can substances which would not affect patient and thus less prone to abuse. In a paper published in Addictive Behav- replace a harmful substance with a safer management or for which implications for For example, in more than 30,000 patient ior, Marian Wilson and colleagues at Wash- one. This approach is known as “harm re- patient management are unclear. For ex- years of randomized control trial data of ington State University reported that fre- duction.” Mainstream medicine employs ample, experts noted that there might be nabiximols (Sativex), a standardized can- quency of cannabis use heightened the two opioid drugs as harm-reduction al- uncertainty about the clinical implications nabis extract from GW Pharmaceuticals, associations between pain and depression ternatives in treating opioid dependence: of a positive urine drug test for Tetrahydro- there has been no evidence of abuse or di- and pain and anxiety. Methadone and Buprenorphine (synthetic cannabinol (THC).” version. Wilson’s team interviewed 150 patients opioids that hardly cause a high). The CDC seemed to be advising doctors In 2014, Marcus Bachhuber and col- being treated for Opium Use Disorder at a Bupenorphine combined with an opioid that opioid users should not be discouraged leagues published a study in the Journal medication-assisted treatment clinic. “Re- blocking drug called Naloxone, is sold as from also using cannabis. Unfortunately, of the American Medical Association that sults from the current study,” they wrote, Suboxone. These two drugs are the corner- this sensible advice has not been widely evaluated various attempts to reduce opi- “may indicate that cannabis use interferes stone of “Medication Assisted Treatment,” heeded. Cannabis clinicians frequently oid dependence and overdose deaths. One with one’s ability to unbundle one’s exist- an approach to opioid abuse that combines encounter patients who report, “my pain approach was a prescription-drug monitoring symptoms. Cannabis may decrease FDA-approved drugs (courtesy of the management doctor found THC in my ing program adopted by most states that confidence for managing emotions, or di- same industry that started this problem) urine, and they kicked me out of their prac- enables a medical provider to log in, look minished ability to manage symptoms may with counseling and behavioral therapies. tice.” Or, “they cut off my prescriptions up a patient, and find out which controlled increase frequency of cannabis use.” How effective are Methadone and Sub- with no taper.” substances they’ve been prescribed, where Why do my patients consistently report oxone? A 2014 review by the Cochrane This punitive approach makes no sense. and when the prescriptions were filled, and and demonstrate enhanced confidence? Database on the efficacy of these harm-re- It is well documented that cannabis is so forth. The monitoring program was not They specifically tell me that they’re better duction options found that only high-dose a good replacement for both illegal and associated with decreased opioid overdose able to unbundle their symptoms. Without buprenorphine (16 mg) was more effective prescription drugs. A survey of 473 medi- deaths. cannabis it’s “one big ball of suffering”; than placebo in suppressing illicit opioid cal cannabis patients in British Columbia Laws requiring or allowing a pharma- but in that cannabis state of consciousness use. Methadone was found to have equal found 87 percent were using cannabis as cist to request patient identification were they can say, “Okay, that’s the sensation, efficacy in suppressing illicit use, and was a substitute for something else —80.3 per- found to have no association with the rate and here’s the judgment. I call that pain. superior to Buprenorphine in retaining cent using it as a substitute for prescription of opioid overdose deaths. Increased state And here’s the anxiety about that pain.” people in treatment. drugs; 51 percent for alcohol; 32 percent oversight of pain management clinics also That unbundling is extremely therapeu- It’s important to note that while suppress- for illicit substances. The reasons they gave demonstrated no significant impact. tic. Why are my patients different from the ing illicit opioid use is the goal, retaining were: more effective, fewer and less severe But states that simply passed a medical patients in the cohort of the study? people in treatment may alone be a helpful side effects, lower risk of dependence and cannabis law, reduced opioid overdose I think there may be a selection bias in outcome. Conversely, many critics point addiction. deaths by 24.8 percent on average! that the people coming to me are motivat- out that Suboxone is effective at suppress- Several other studies have shown similar The paper by Bachhuber et al inspired ed. They are early medical cannabis adopt- ing the most unpleasant aspect of opi- results. “replication studies” by a RAND Corpora- ers. They want to use cannabis to get off oid addiction and abuse – the withdrawal Patients with “Opioid Use Disorder” tion group led by Rosalie Liccardo Pacula. opioids. symptoms– which simply allows addicts to There is strong evidence that cannabis They reporterd in the Journal of Health feel well until they can get another dose of can be safely used to reduce and replace Economics that access to legal cannabis their drug of choice. opioid medications in patients with chronic Self-efficacy is the belief in dispensaries was the key factior in driving Both drugs can lead to overdose deaths. pain. What about patients with “Opioid Use one’s ability to succeed at a giv- down opioid-related mortality. Methadone was responsible for about one- Disorder” who don’t have chronic pain? Pacula reported a corollary finding: Unfortunately, the clinical evidence is en task, a ‘can-do’ attitude, a scant, but some data plus the anecdotal re- sense of optimism and control ports of patients and clinicians on the front over one’s environment. lines supports more research in this area. Naltrexone, a drug that blocks the opioid Wilson and colleagues also published an receptor, is another medication-assisted abstract this year in the Journal of Pain, approach to opioid abuse, but in this case, with a different cohort: 150 people with a way to support opioid abstinence. Canna- opioid use disorder, and another 150 peo- bis use has been associated with improved ple with persistent pain. Naltrexone treatment retention. This time they controlled for “self-effica- A 2009 study from Wilfrid Raby and col- cy.” They found that cannabis users had leagues at Columbia University in New more confidence, better sleep quality and York found that intermittent cannabis us- less pain intensity. ers were staying in a treatment program “Self efficacy” is the belief in one’s abil- for 113 days, on average, whereas people ity to succeed at a given task, a ‘can-do’ who didn’t use cannabis at all only lasted attitude, a sense of optimism and control 47 days. The investigators also found that over one’s environment. It determines intensive behavioral therapy helped the whether or not one can rise up after being consistent cannabis users but didn’t help knocked down. Improving self-efficacy is the non-users at all. an important goal, because people with Other studies have shown that THC re- higher levels of self-efficacy tend to be duces opioid withdrawal symptoms and more successful reducing opioid use by us- cannabis users are more likely to come ing cannabis —and more successful over- back for a second injection of long-acting all. naltrexone, and that opioid injectors who Might a certain dose and frequency of use cannabis have lower monthly injec- cannabis use enhance self-efficacy, while a Prince Rogers Nelson, a brilliant musician who lived with chronic pain (and had a tions than their non-cannabis using peers. higher dose and frequency reduce it (by valid medical diagnosis), died of an opioid overdose in April 2016. He did not know Cannabis can not only keep people in fostering reliance on cannabis instead of that the Vicodin that an associate obtained for him had been laced with fentanyl. treatment, replace and reduce opioid in- continued on next page O’Shaughnessy’s • Autumn 2018 —37—

Cannabis/Opioids from previous page one’s self)? Field-grown plants vs. synthetic and processed alternatives es heroin-seeking behavior in animals, and In cannabinoid medicine we see many bi- reduces heroin-related cue-induced crav- directional effects —cannabis producing ing in human heroin abusers. And it can do one result or the opposite result, depending all this without any of its own rewarding on dose, frequency, and “set and setting,” properties, so it has no abuse liability. meaning the attitude of the person and the environment in which they use it. If you take the same dose of cannabis on Laws need to change so the your couch with a friend, versus at the oral medical community can start us- surgeon’s office, you’re going to have a ing cannabis as an adjunctive different experience with it. Could there be a way to approach cannabis use that would treatment for opioid use disorder. enhance self-efficacy? I believe the answer Tobacco is a healing herb. Tobacco products are the leading cause of morbidity, mortality, What is to be done? is yes, especially if we give it to patients and healthcare spending. Doctors and patients need better access to with that intention. medical cannabis, especially standardized, There are big populations of people who dependable formulations containing both haven’t heard about using cannabis to re- CBD and THC. Laws need to change so duce opioid use. They have low self-effica- the medical community can start using cy. They don’t love or know about canna- cannabis as an adjunctive treatment for bis. They’re not fed up with the medical opioid use disorder. We’re thankful that we system. They still trust the people giving have a great medical cannabis system in them methadone. What can we learn from Maine, for example, but as of September our patients, our successes, and help apply 2018, CHECK THIS, I am still not allowed that to the rest of the population? to use cannabis to treat patients with opioid use disorder unless they have chronic pain When we get to the roots of the that’s failed to respond to six months of opioid problem, we’re getting to the conventional therapy. There are still many roots of many other problems that parts of the country and the world where are leading to morbidity, mortality, cannabis is still completely illegal. Some addiction experts are concerned and more healthcare spending. Poppies yield natural opioids. Oxycontin is a semi-synthetic derived from thebaine. that liberalizing the cannabis laws will encourage adolescents to perceive it as safe If we want to solve a problem that’s kill- and to start using at a younger age. ing 115 Americans a day, we have to get to A 2015 paper in Lancet Psychiatry pro- the roots of it. And when we get to the roots vided reassuring data. “There is no evi- of the opioid problem, we’re getting to the dence of a differential increase in past roots of many other problems that are lead- month use in youths that can be attributed ing to morbidity, mortality, and more to state medical marijuana laws,” it con- healthcare spending. cluded. The CBD Era And a paper in The International Journal The medical cannabis movement has led of Drug Policy found “the results of this to a whole new set of cannabis users —pa- study showed no evidence for an increase tients who want symptom relief. They want Organic vegetables are available at Farmers Markets for a forunate fraction of the US popu- in adolescent marijuana use after the pas- the medical benefits, but they don’t want to lation. Supermarket aisles are filled with processed foods. sage of state laws permitting use of mari- get high or impaired. Fortunately, in 2008 juana for medical purposes. Concerns that the advent of analytical labs enabled grow- cannabinoid. reduces anxiety, a component of abuse and increased marijuana use is an unintended ers to identify cannabis strains in which CBD been shown to reduce the side ef- relapse. CBD has been shown to reduce effect of state marijuana laws seems un- non-impairing cannabidiol —CBD, a sister fects of THC and to enhance its benefits. It the rewarding properties of opioid drugs founded.” molecule of THC— was the predominant has minimal side effects and toxicity, and and opioid withdrawal symptom. It reduc-

Cannabis dosing to support opioid reduction Case Report: Cannabis Replacing Opiods for Chronic Pain Cannabis can be used in so many different ways to individually tailor a treatment depending on one’s needs. Could specific approaches to dosing further increase the A 43-year-old man with chronic pain, victim of a hit-and-run motor vehicle-pedes- effectiveness and reduce the potential harm of cannabis in the setting of opioid depen- trian accident at age 25, resulting in spinal disc herniation. When he first came in he dence? Here are the guidelines I provide to my patients in Maine: had already tried cortisone injections, chiropractic, physical therapy, and prescrip- 1. Always take a small dose of cannabis, preferably using a non-inhaled delivery tion medications. He did not have satisfactory improvement. He saw an orthopedic method, with every dose of opioids. Many people make the mistake of thinking they specialist who recommended surgery based on the patient’s physical exam, which should choose one or the other, but it’s clear for all the reasons discussed in this article included weakness in one of his legs that was affecting his gait and posture. The that the combination works best. In most people, only a low dose of THC is needed to patient did not want surgery at age 43; he wanted to postpone it as long as possible. augment the effects of the opioids, so I instruct my patients to start at one-to-two mil- He was a high school graduate and worked at an electronics store. He had a lograms of THC per dose and gradually increase until they notice the opioid pills are 15-month old, first-born child. He came in with an average pain level of 6-7 out of starting to feel much stronger. Once reaching this dose of THC, many will begin taper- 10. He had a little cannabis history, had tried it at age 16, but hadn’t used it in 20 ing the opioid drugs by cutting tablets in half and/or taking them less frequently. years. He didn’t have any history of adverse affects with cannabis. He simply wasn’t using it. He was on muscle relaxants, two anti-inflammatories, two opioid pain reliev- 2. Use inhaled cannabis to manage breakthrough symptoms and to reduce cravings. ers (tramadol and hydrocodone), an anti-nausea drug because the pain relievers cause The rapid onset of vaporized or smoked cannabis makes it perfect for addressing these nausea, blood pressure medication, and cholesterol medication. He had previously challenges that so often interfere with successful opioid tapering. I encourage my tried gabapentin (an anti-convulsant often used to treat pain) and Lyrica, which is in patients to reserve inhaled cannabis for when it’s needed most, ideally three times that same category. daily or less, and to use the lowest effective dose, taking one ortwo puffs and repeating At a return visit six months after cannabis certification, he reported started using ed- every five minutes as needed, to prevent building tolerance to cannabis. ible cannabis in the form of cookies – not something I typically recommend. I prefer 3. Use cannabis to promote regular sleep patterns. Reducing and discontinuing opi- products that enable you to know how many drops you’re taking or how many mil- oid drugs is a challenge at every level of our being: physical, mental/emotional, and ligrams. The patient was also smoking cannabis two to three times weekly, just taking spiritual. There is no medication or herb that can make this easy, and people dedicated two to three puffs for breakthrough symptoms. Initially he had an adverse affect from to this change need every ounce of strength, determination, and resilience they can the edible —he ate too much— but once he adjusted the dosage he was able to use the muster. This is why restorative sleep is essential and should be addressed at the begin- cookies without any side effect. ning of this process. Only sedating strains of cannabis should be used in the evening, At six months, he had stopped hydrocodone and tramadol, the two opioids, and and an oral dose of cannabis (e.g. capsule) should be taken before bed if needed. also stopped one of the anti-inflammatories. The anti-muscle-spasm medication that While proper use of cannabis is often enough for most people to achieve healthy sleep, he had been using daily was now needed only once a month. His average level was the cannabis can also be safely used in conjunction with other natural and pharmaceu- down to 3-4 on the pain scale. He had a significant decrease in muscle spasms. tical sleeping aids. His physical exam revealed improvement. He had normal strength in his lower ex- 4. Use cannabis to enhance health-promoting activities such as exercise, meditation, tremities and was actually walking normally. Perhaps that’s because he had improved prayer, journaling and reflecting, and counseling or behavioral therapies. As men- function, or because the muscle spasms had been under control for so long his spine tioned above, the enhanced neuroplasticity of the endocannabinoid system can help was able to get back into alignment, or because cannabis has anti-inflammatory prop- these essential components of a healing plan work even more powerfully. Many of my erties and reduced the inflammation that was pressing on that nerve root. Probably all patients find themselves more likely to participate in these activities when they’re of the above. He reported that he was able to carry his son, was able to enjoy father- combined with cannabis. So when using inhaled cannabis to treat breakthrough symp- hood. And that’s an incredible result! toms or cravings (suggestion 2), I tell my patients to take a walk outside, try some of When I was in my medical training, if I would have seen that happen, I would have my free exercises and meditations on Healer.com/wellness, or sit down with their thought I was in some alternate reality. How did this patient get such good results? How did he actually come off of all his opioids and medications? This is normal for us now. We see this all the time. —Dustin Sulak, D.O.