01/10/17

Marijuana Makes You Nauseous?

© Viachaslau Vaitsenok |123rf.com

Live Science reported on a study published in the August 31, 2016 issue of The Lancet that found more people are using marijuana and they are using it more often.  In 2014, 13.4% of people said they had used marijuana in the previous year, an increase of 3% since 2002. The percentage of people who reported daily or near daily use rose from 1.9% to 3.5%. At the same time concerns about the risks associated with marijuana use dropped. In 2002, 50.4% of adults thought there was a great risk with marijuana use. That fell to 33.3% by 2014. But the perception of lowered risks may be premature.

The authors of the Compton et al. study thought the combination of increased marijuana use and a decreasing perception of the harm suggested there was a need for education regarding the risks of smoking marijuana. One of these health risks is for a medical condition called cannabinoid hyperemesis syndrome, or CHS. It is caused by heavy, long-term use of various forms of marijuana. Its symptoms include cyclic episodes of nausea and vomiting; some people have severe abdominal pain. A CBS Evening News report described a man who struggled with symptoms of CHS for two years before it was correctly diagnosed. Oddly, hot showers or baths seem to provide symptom relief.

CHS was first reported in 2004 by Allen et al. The ten patients were all cyclical vomiters and chronic marijuana users. Nine of the ten also had the abnormal bathing behavior of multiple hot showers or baths. The symptoms of nausea, vomiting and abdominal pain would all settle within minutes of taking a hot bath or shower. Symptoms resolved with abstaining from marijuana use in seven of the ten patients. Three of the abstaining patients resumed marijuana use and relapsed within months.

High Times described CHS as a rare form of cannabinoid toxicity that developed in chronic smokers. The author suggested with CHS, there was generally daily use in excess of three to fives times for several years. CHS is often mistaken for cyclic vomiting syndrome (CVS), because the symptoms are similar. But CVS is not caused by marijuana use. CHS is easily cured by abstaining from cannabis use.

This should not, by any means, hurt marijuana’s reputation for being the safest recreational drug around, but people need to be aware of the syndrome’s existence. If you know anyone with these symptoms tell him or her go to a doctor and stop smoking.

A 2011 review article by Galli et al., “Cannabinoid Hyperemesis Syndrome,” observed how the recognition of CHS coincided with the increased use of cannabis. Their review gave an overview of cannabinoid pharmacology that focused on the properties that seem to contributes to CHS. They also gave a clinical description of CHS and a proposed a method for clinical evaluation, which included differential diagnosis and treatment modalities.

Patients are typically young adults with a long history of cannabis use. They present with recurrent episodes of nausea, vomiting and dehydration with frequent visits to emergency departments. In almost all cases, there was a delay of several years between their chronic marijuana use and the onset of symptoms. One study reported an average duration of 16.3 years of cannabis use before the onset of symptoms. But there have been reports where the time lag was equal to or less than three years.

CHS is a recurrent disorder, with symptom-free periods. There are three phases: pre-emetic, hyperemetic, and recovery. The pre-emetic phase can last for months or years. Patients have early morning nausea, a fear of vomiting and abdominal discomfort. They maintain normal eating patterns and may even increase their marijuana use because its reported relief of nausea.

The hyperemetic phase has spasms of intense and persistent nausea and vomiting, which has been described as “overwhelming and incapacitating.” Patients vomit profusely, often without warning—up to five times per hour.  There can be weight loss. Most patients have diffuse, but relatively mild abdominal pain. They are found to be dehydrated, but hemodynamically stable. The tests and work ups done at EDs are inconclusive in the majority of cases.

During this phase, patients take numerous hot showers throughout the day. As this seems to be the only measure that brings some symptom relief, it rapidly becomes a compulsive behavior. The precise mechanism for this relief is not known. It typically lasts for 24 to 48 hours, but the risk of relapse is high if the patient resumes cannabis use.

The recovery phase can last for days, weeks or months. It’s associated with relative wellness and eating patterns. “Weight is regained and bathing returns to regular frequency.”

Patients with CHS usually are misdiagnosed for a considerable length of time. One problem is that it is often confused with cyclic vomiting syndrome (CVS). “Confusion also exists in the medical literature secondary to a failure to recognize chronic marijuana use as a source of vomiting.” Although there is a close similarity of conditions, there are also significant differences.

A 2015 study by Kim et al. looked at the prevalence of patients presenting for cyclic vomiting in Colorado before and after the liberalization of medical marijuana in 2009. A secondary objective was to describe the odds of marijuana use among cyclic vomiting visits during these same time periods. The prevalence of CVS increased from 42 per 113,262 Ed visits to 87 per 125,095 ED visits after marijuana liberalization. Patients with CVS post liberalization were more likely to have documented marijuana use than patients in the pre liberalization period.

The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.

The study said it does not demonstrate causation of CHS. But it does demonstrate a preliminary association “and should serve as the foundation for future prospective studies on the association between marijuana and cyclic vomiting, the eventual establishment of formal diagnostic criteria for CHS.” Foremost among the interventions for symptomatic treatment should be counseling toward abstinence from marijuana use. The authors saw their study as a crucial first step towards establishing a formal diagnosis of cannabinoid hyperemesis syndrome.

High Times seemed to minimize the present concerns with CHS by referring to it as “a very rare syndrome” that is easily cured. CHS does not reverse marijuana’s reputation as “the safest recreational drug around” at this point. But remember that even High Times agreed the cure for CHS is to stop using cannabis. We are just entering into a time of not only increased marijuana use, but also increased daily or near daily marijuana use. As this trend grows into a population of chronic, heavy marijuana users, the safety profile for marijuana will likely change; and it seems that CHS will be part of that decreasing safety profile.

07/27/15

Clearing Away the Medical Marijuana Smoke

© lunamarina | stockfresh.com

© lunamarina | stockfresh.com

There have been some studies that demonstrate potential medicinal benefits of marijuana use, but they often don’t meet the clinical trial standards used by the FDA to approve medications for human consumption. With the state-by-state movement to legalize marijuana progressing, there is a need for quality scientific research into the potential medical benefits of marijuana. Although marijuana has been used recreationally and medicinally for centuries, the mechanics of how it works are not clearly understood. This is partly because there are over 400 different chemicals in cannabis. THC, the psychoactive ingredient in cannabis, was just isolated in the 1960s. What follows are reviews of some articles that look at the benefits and the concerns with medical marijuana.

Marijuana has been used as a folk medicine as far back in time as five thousand years ago. The first medical use likely occurred in Central Asia and spread from there to China and India. The Chinese emperor Shen-Nung is known to have prescribed it in 2800 BC.  Between 2000 and 1400 BC it came to India, and from there to Egypt, Syria and Persia. The Greeks and Romans valued marijuana as hemp for ropes. Europeans ate its seeds and used its fibers to make paper. An urban legend falsely held that the U.S. Constitution, Declaration of Independence, and Bill of Rights were written on hemp paper. All three were actually written on parchment.

An Irish doctor, W. B. O’Shaughnessy, working in Calcutta in the 1830s, wrote a paper on the medical uses of cannabis, which were strikingly similar to those known today—vomiting, convulsions and spasticity. By 1854, the medical use of cannabis was listed in the US Dispensatory. Nineteenth-century physicians had cannabis tinctures and extracts for ailments from insomnia and headaches to anorexia and sexual dysfunction. “Cannabis-containing remedies were also used for pain, whooping cough, asthma, and insomnia and were compounded into extracts, tinctures, cigarettes, and plasters.”

The above short history on the history of medical marijuana was taken from an article by J. Michael Bostwick, “Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana.” He noted how the term medical marijuana refers to botanical cannabis, which contains hundreds of compounds—including the two most often used medicinally, THC and cannabidiol. Synthetic cannabinoids are produced in a laboratory. Botanical cannabis attracts the notoriety and controversy—because it is the same substance used recreationally by “stoners” to get high.

Bostwick noted how the recreational and medical marijuana use of marijuana is not always distinct, which has medical implications for both seasoned and naïve users. For example, naïve users may decide to stop using medical marijuana because of the psychoactive effects of the THC. Although most users will experience a mild euphoria, a few experience dysphoria, anxiety and even paranoia.

As cannabis strains are bred that amplify THC content and diminish counteracting cannabidiol, highs become more intense but so do degrees of anxiety that can rise to the level of panic and psychosis, particularly in naive users and unfamiliar stressful situations.

The Bostwick article reviewed the often-blurred relationship between medical and recreational users. He discussed a Canadian study that found medical cannabis use often followed recreational use; and that most medical users continued using marijuana recreationally.  Another study of 4100 Californians found that medical users preferred inhaling their medication. Smoked cannabis has a more rapid response and is easier to titrate so that users get the analgesic effects without the higher levels favored by recreational users seeking the high. Given some of the medical problems from smoking marijuana, using vaporizers or nasal sprays may be an effective alternative delivery system.

Doctor Robert DuPont, in his book The Selfish Brain: Learning from Addiction, referred to marijuana as “a crude drug, a complex chemical slush.” Marijuana and hashish contain over 420 different chemicals, falling into 18 different chemical families. THC and cannabidiol (CBD), are only two of sixty-one cannabinoids, chemicals found only in the marijuana plant. THC is highly soluble in fats, and this quickly passes the blood-brain barrier. The factor, plus the fact that it is insoluble in water, means that it is trapped in bodily organs like the brain and reproductive glands, remaining there of days or even weeks afterwards.

Grant et al. reviewed evidence on the medicinal usefulness of marijuana in “Medical Marijuana: Clearing Away the Smoke.” They noted that most of the studies on the efficacy and safety of cannabinoids for pain and spasticity have occurred since the year 2000. A series of randomized studies at the University of California Center for Medicinal Cannabis Research (CMCR) found that cannabis significantly reduced pain intensity. A significantly greater proportion of individuals reported at least 30% reduction in pain on cannabis; the threshold of decreased pain intensity generally associated with improved quality of life. Medium doses of 3.5% THC cannabis cigarettes were as effective as higher dose (7% THC).

Oral preparations of synthetic THC (dronabinol, Marinol) and a synthetic THC analogue (nabilone, Cesamet) are legally available. Studies suggest that dronabinol significantly reduces pain. The effects on spasticity are mixed: “there may be no observable change in examiner-rated muscle tone, but patients report significant relief.” There has been less research done with nabilone, but there have been reports of modest analgesia. Dronabinol and nabilone are FDA-approved for control of acute and delayed nausea and vomiting from cancer chemotherapy.

Alternative delivery systems for cannabis include vape-pens, sublingual devices, and others that use a metered spray device. The advantages to such systems seem to be the use of known cannabinoid concentrations, predetermined dosing portions, and time-out systems that may help prevent overuse.

There are side effects, which are dose-related in terms of severity. Grant et al. reported that they seem to decline over time and are of mild to moderate severity. “Reviews suggest the most frequent side effects are dizziness or lightheadedness (30%-60%), dry mouth (10%-25%), fatigue (5%-40%), muscle weakness (10%-25%), myalgia [muscle pain] (25%), and palpitations (20%).” There is little data on a timeline of adverse or therapeutic effects. There have been concerns that rapid tolerance to adverse effects may indicate a corresponding tolerance to beneficial effects. But studies of oral sprays in multiple sclerosis report that you can reduce the incidence and severity of adverse effects by downward self-titration without loss of analgesia.

There are additional adverse effects, including some psychiatric side effects, especially with cannabis having high concentration of THC. See the original article for more specifics. The longer-term health risks of medicinal cannabis are unclear; most of the current evidence is based upon non-medical use. Some medical professionals indicate that effective medicinal use of cannabis requires significantly less marijuana than is typically consumed by recreational users.

In “The Current Status of Medical Marijuana in the United States,” Doctor Gerald McKenna noted how the majority of medical marijuana users in Hawaii claim they have chronic pain. He said a main problem in getting the medical profession to support the use of medical marijuana is that it is not widely used medicinally in a non-smoking form. “Authorizing use by inhalation of a drug with an unknown number of co-drugs contained in the same raw form is not supportable.” He said that supporting the use of medical marijuana by inhalation because users prefer it is akin to supporting the inhalation of any other drug taken orally. His impression is that medical marijuana laws have been passed “to bypass the illegality of marijuana.”

He did recommend removing marijuana from Schedule I controlled substance so research could be done more easily. “Until that research is done, stating that marijuana is useful for treating chronic pain, anxiety, post-traumatic stress disorder, depression, and other health conditions remains anecdotal and conjectural.”

It has become clear that the federal government needs to modify its resistance to reclassifying marijuana’s Schedule I Controlled Substance status to allow more quality research into its use and to fund that research. Otherwise, the current circus of inconsistent regulations from state to state, and unverified claims about the medicinal benefits of marijuana will have us back in the days of patent medicines, as far as marijuana is concerned. Further reflections on medical marijuana can be found in: “Let’s not Get Ahead of Ourselves,” “Is the Cart Before the Horse?” and “Marijuana Peek-a-Boo.”

11/17/14

The Improbable Truth of Sudden Death with Marijuana

iStock image

iStock image

A study by German researchers, “Sudden Unexpected Death Under Acute Influence of Cannabis,” has stirred up a firestorm of controversy as a result of their conclusion that two unexplained deaths were the result of marijuana use. High Times ridiculed the study as another round of “Pot Kills” propaganda. They claimed that news sources like Mail Online were “bastardizing” the story and spreading a certain level of fear. High Times and other news sources then quoted the head of the German Association for Drugs and Addiction (FDR) as saying that cannabis does not paralyze the breathing of the heart. “Deaths due to cannabis use are usually accidents that are not caused by the substance, but to the circumstances of the use.” But let’s take a look at what the study and the researchers actually said.

The case report (here and here) described two young, healthy men who died unexpectedly under the acute influence of cannabinoids (THC). “To our knowledge, these are the first cases of suspected fatal cannabis intoxication where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical, and genetical examinations, were carried out.” After excluding other possible causes of death, they assumed the men died from “arrhythmias evoked by smoking cannabis.” HOWEVER, “this assumption does not rule out the presence of predisposing cardiovascular factors.”

They noted the absolute risk of cannabis-related cardiovascular effects was low and that the cannabis-induced changes were transient. Yet they cited two studies indicating that the risk of myocardial infarction was elevated almost 5 times in the first hour after smoking marijuana; then it declined rapidly afterwards. “Consequently, the relative risk of cardiovascular effects is most probably increased within this period.”

The Mail Online article cited the research claims of the German study, namely that cannabis can kill, but also stated that: “it remains unclear how it can trigger heart problems.”  They pointed to more significant risks associated with marijuana use and quoted David Raynes of the UK National Drug Prevention Alliance as saying about the study’s findings: “These deaths are rare and will remain rare. The real risks are from long-term effects on the young brain.”

There was another alleged case of unexplained death from THC, a young woman named Gemma Moss. A Colorado doctor who works with medical marijuana patients in that state said: “There’s no history of any reports of a death from cannabis ever.” He admitted that it could cause an increased heart rate, so there was a potential problem with someone with a pre-existing heart disease. “But there’s no known dose of cannabis that could kill a human.”

Well, there does seem to be a known dose of THC that would kill a human. The above noted report cited a 2009 study in American Scientist on the toxicity of recreational drugs suggested that using more than 1,000 times the effective dose of THC in marijuana would have to occur for possible fatalities. This fact—that typical doses of THC are well below the supposed lethal dose—was also noted by the German researchers. But they suggested further study of the potential issue and cautioned against individuals who are at high risk of cardiovascular disease to avoid the use of cannabis.

It is impossible to predict how certain individuals respond to cannabis smoke, as underlying illnesses and complicating factors may be unknown. The presented case highlights the potentially hazardous cardiovascular effects of cannabis in putative healthy young persons.

The researchers had an approach that Sherlock Holmes would have been proud of. They said: “After exclusion of other causes of death we assume that the young men died from cardiovascular complications evoked by smoking cannabis.” Holmes famously said: “When you have eliminated the impossible, whatever remains, however improbable, must be the truth.” It seems to me that pro-marijuana individuals and organizations are dismissing the results of the study out-of-hand for their own propaganda purposes.