Autumn 2005
O'Shaughnessy's
Journal of the California Cannabis Research Medical
Group
|
Marijuana and Impairment
By Richard Bayer, MD
Does cannabis alone, inhaled eight or more hours before activities
such as driving a vehicle or working with machinery, cause significant
mental or motor impairment that might increase risk to self or others?
This is the question that Oregon legislators should have considered
during the session just ended.
Instead, the Republican-controlled House passed a bill that would allow
employers to fire —without evidence of impairment— workers
who register with the Oregon Medical Marijuana Program and who use
marijuana as medicine. Fortunately, the house bill failed in a Democrat-controlled
Senate committee after heated testimony, but this may be a temporary
reprieve as this legislation will probably be introduced again in the
next round.
The scientific evidence
Cannabis has been used to relieve pain for centuries throughout the
world, including the US, prior to the enactment of the Cannabis Tax
Act of 1937.1 Cannabinoids are a category of substances with cannabis-like
properties and include the natural cannabis plant, synthetic cannabinoids,
and internal (endogenous) hormones that mimic cannabis.
Case reports of the benefit of smoked cannabis to relieve pain are
published.2 The major psychoactive cannabinoid, THC, is as effective
as codeine for relieving pain. Researchers wrote, “This trial
has demonstrated an analgesic [anti-pain] effect of THC in patients
with cancer pain.”3 Experiments with monkeys and rats show unequivocal
science for the analgesic effect of cannabinoids in laboratory animals.4
Endogenous cannabinoids are important in pain control.5 GW Pharmaceuticals
has performed randomized double-blind placebo-controlled trials showing
Sativex, a cannabis extract administered under the tongue, markedly
improves pain and muscle spasm.6 Canada recently approved Sativex for
treating pain with applications pending in the US and other countries.7
The International Association for Cannabis as Medicine (IACM) lists
dozens of clinical studies including studies on pain.8 Perhaps the
best summary is from the prestigious Institute of Medicine, “In
conclusion, the available evidence from animal and human studies indicates
that cannabinoids can have a substantial analgesic effect.”9
The Oregon Medical Marijuana Act passed in 1998 states, “The
people of the state of Oregon hereby find that: (1) Patients and doctors
have found marijuana to be an effective treatment for suffering caused
by debilitating medical conditions, and therefore, marijuana should
be treated like other medicines.”10 This means Oregonians voted
to make medical marijuana treated like medical morphine, medical synthetic
THC, or Food and Drug Administration-approved medicines.
An inhaled medicine typically works faster but the effects usually
do not last as long as a medicine taken by mouth that must be absorbed
by the digestive tract.
The psychoactive effects of both synthetic THC (Marinol) and herbal
marijuana are due primarily to THC.11 The timing issues about how a
drug behaves in the body are called pharmacokinetics and are mostly
dependent on the method of administering the drug. For example, an
inhaled medicine typically works faster but the effects usually do
not last as long as a medicine taken by mouth that must be absorbed
by the digestive tract. Inhaling cannabis through smoking or vaporizing
cannabis bypasses the digestive tract.
In “A Primer of Drug Action,” pharmacologist Robert Julian,
MD, PhD, states, “absorption of inhaled drugs is rapid and complete.
The onset of behavioral effects of THC in smoked marijuana occurs almost
immediately after smoking begins and corresponds with the rapid attainment
of peak concentrations in plasma. Unless more is smoked, the effects
seldom last longer than three to four hours.”12
In “Clinical Pharmacokinetics of Cannabinoids” Franjo Grotenhermen,
MD, wrote, “Pulmonary [lung] assimilation of inhaled THC causes
a maximum plasma concentration within minutes, while psychotropic effects
[the “high”] start within seconds to a few minutes, reach
a maximum after 15 to 30 minutes, and taper off within two or three
hours.”
Grotenhermen states, “The peak psychotropic effects (‘high’)
after intravenous and inhaled THC application were noted after 20-30
minutes and decreased to low-levels after three hours and to baseline
after four hours (Hollister et al 1981, Lindgren et al 1981, Chiang
and Barnet 1984)... Hence about one to four hours after smoking there
is a good correlation between plasma level and effects (Chiang and
Barnett 1984). There was also a good correlation between THC plasma
levels and other effects in this phase, with heart rate (Cocchetto
et al 1981) and with psychomotor impairment (Barnett et al 1985).” In
summary, this peer-reviewed scientific article informs us that the
impairment resolves when plasma THC levels return to low-levels at
three hours and baseline around four hours after smoking marijuana.13
Since THC acts identically whether synthetic or herbal, we should look
at the warnings section of the US Food and Drug Administration (FDA)-approved
dro-nabinol (synthetic THC marketed as Marinol): “WARNINGS: Patients
receiving treatment with Marinol should be specifically warned not
to drive, operate machinery, or engage in any hazardous activity until
it is established that they are able to tolerate the drug and perform
such task safely.”14 This is sound advice.
In the above studies, impairment from smoked cannabis or marijuana
resolves within four hours. Since synthetic THC and herbal THC are
identical once inside the body, there is no scientific rationale for
discrimination against those who prefer medical THC from an herbal
rather than a synthetic source. The Marinol package insert warnings
should be heeded regardless of whether a person uses synthetic FDA-approved
THC (as in Marinol) or herbal THC (as in marijuana or cannabis).
When a clinician monitors drug therapy, s/he educates a patient through
a careful explanation of the procedure (method of use and expected
results), alternative therapies, and risks involved in using or not
using the medicine. There are many medicines —prescription or
non-prescription— that cause drowsiness or impairment. These
include medicine for blood pressure, diabetes, arthritis, respiratory
infection, allergies, mood stabilization, and pain. Physicians and
patients use good communication to lessen risks of adverse drug reactions.
It is important to avoid impairment when driving, operating machinery,
or engaging in any hazardous activity whether in the workplace or not.
Monitoring by family, friends, peers, and co-workers for anyone’s
impairment can improve safety. One reason that direct observation of
impairment is important is that impairment can be caused by health
problems not related to prescription medicines. Things like non-prescription
over-the-counter medicines, acute influenza, or a family emergency
resulting in lost sleep can cause impairment. This means good communication
between employees and employer can lessen risk of impairment at work.
Urine drug testing to monitor therapy is not routinely used in clinical
medicine. It is helpful in toxicology or poisoning cases when a doctor
is uncertain what drugs are in the body. Urine tests are also used
in medical-legal settings. The standard urine test for “marijuana” does
not test for the “parent drug,” THC, but tests for an inactive
non-psychoactive metabolite or breakdown product of THC.
Inactive breakdown products in a standard “urine marijuana test” can
remain positive for weeks to months after consuming cannabis, even
when there is no impairment.
Inactive breakdown products in a standard “urine marijuana test” can
remain positive for weeks to months after consuming cannabis, even
when there is no impairment. The US Department of Transportation commented
about urine drug testing that, “while a positive urine test is
solid proof of drug use within the last few days, it cannot be used
by itself to prove behavioral impairment during a focal event.” 15
In other words, urine drug testing does not prove impairment, it only
proves recent use.
Flight-simulator studies
Between 1976 and 1991, there were at least four flight-simulator
studies published according to a Library of Medicine search. One
showed impairment
for at least two hours that resolved by four to six hours.16Three
others by a different research team showed conflicting results. Two
of those
three show some impairment at 24 hours,17, 18while one of the three
studies showed abnormal flight simulator results only at four hours
but none at eight or 24 hours.19 Another unpublished study by the
same group failed to find impairment, bringing the total studies
to five.
These mixed results create confusion. Since blood levels of THC are
near baseline four hours after smoking cannabis and impairment beyond
four hours cannot be consistently demonstrated, the researchers actually
call this flight simulator result a “hangover effect” rather
than intoxication. According to Dr. Leirer, the purported hangover
effect is “very marginal” and is only detected in tests
of “very complex human/machine performance.” Comparable
subtle effects are reported at very low blood-alcohol levels of 0.025%,
which is well below the .04% level allowed in commercial motor vehicle
drivers.20
Possibly because of confusion surrounding flight simulator data,
other researchers study actual motor vehicle accidents. In 2002,
authors
Gregory Chesher and Marie Longo concluded, “At the present time,
the evidence to suggest an involvement of cannabis in road crashes
is scientifically unproven.” 21 However as they note, some of
this may be because of evolving science. As mentioned above, testing
for inactive urine metabolites does not test for impairment. Recent
studies continue to show that “no increased risk for road trauma
was found for drivers exposed to cannabis.” 22
But there is also an effort to base impairment on measuring the “parent
drug” responsible for impairment, namely THC. Dr. Olaf Drummer,
measured THC levels in fatal crashes in Australia and noticed an association
between high THC levels and risk of traffic fatality even in the absence
of other drugs.23 Based on forensic evidence, he determines whether
a driver is “culpable” or responsible for the fatal accident
and correlates it to blood THC levels. Drummer and colleagues conclude, “Recent
use of cannabis may increase crash risk, whereas past use of cannabis
does not.”24
Grotenhermen’s review of Drum-mer’s work adds, “While
drivers with low concentrations [of THC] in their blood had a lower
probability of causing a traffic accident than drug free drivers, higher
THC concentrations were associated with a considerably higher culpability
ratio.” 25
It remains unclear how to define the gray area about what is “recent” and
what is “past” use of cannabis, even if one supports using
parent-drug blood THC levels as a marker for impairment. This is because
the THC level below which there is no impairment, varies dramatically
among individuals. Plus, the actual numbers of persons who have only
THC in the blood and are involved in accidents is low and studies still
lack adequate statistical significance to draw scientifically firm
conclusions.
Those concerned about legislation suggest that since no culpability
appears to exist below blood levels of 10 nanograms per milliliter
(ng/ml), that any proposed cutoffs be above 10 ng/ml of THC.26 A
study using coordination testing showed inevitable failure on field
sobriety
testing if blood THC levels were 25-30 ng/ml but many failed testing
at 90 and 150 minutes after smoking even though plasma concentrations
were rather low.
The researchers had the foresight to conclude that “establishing
a clear relation between THC plasma concentrations and clinical impairment
will be much more difficult than for alcohol.”27 This is primarily
because alcohol and THC are chemically different and are metabolized
differently inside the body. With passage of medical marijuana laws,
we need additional research to show if there is a correlation between
clinical impairment and blood THC levels. Daily cannabis users (like
patients) can have levels as high as 6 to 10 ng/ml without clinical
impairment even after 24 or more hours of abstinence.28,29 While the
science evolves, most experts think it remains premature to make firm
conclusions about the proper cutoff levels using blood THC for “Driving
Under the Influence” suspicion.30 Proper clinical discussion
of medical marijuana therapy and necessary clinical observation for
impairment remain the primary methods of monitoring for possible adverse
reactions at this time.
In summary, there is no consistent scientific evidence showing any
impairment beyond four hours from smoking marijuana and no scientific
evidence of any increased risk of motor vehicle accidents beyond
four hours after smoking marijuana. As a medical cannabis expert,
I do not
condone any medical marijuana use of cannabis at work. But, private
employer-employee agreements to abstain within four to eight hours
prior to work seem a reasonable type of compromise. This still preserves
safety, and would be consistent with medical treatment plans using
other medicines that may impair.
Registration in the Oregon Medical Marijuana Program should never
be sole cause for termination of employment. Medical use of marijuana
within Oregon law should be treated like medical Marinol, medical
morphine,
and other medications both in and out of the workplace. It is discriminatory
to fire an unimpaired worker whose only cause for firing is registration
with the Oregon Department of Human Services Oregon Medical Marijuana
Program.
References:
1 Tod Mikuriya, MD. Editor of Marijuana: Medical Papers 1839 - 1972.
Medi-comp Press 1973. www.mikuriya.com/mmp.html
2 B Zimmerman PhD, R Bayer MD, & N Crumpacker MD: Is Marijuana
the Right Medicine For You? A Factual Guide to Medical Uses of Marijuana:
Chapter 10. Keats Publishing 1998.
3 R Noyes, F Brunk, D Avery, & A Canter: “The analgesic properties
of delta-9-tetrahydrocannabinol and codeine”. Clinical Pharmacology
and Therapeutics: vol. 18, pg. 84, 1975. www.omma1998.org/Noyes-THC
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4 Deadwyler, Vivian, Meng, Walker, Simone, & Hargreaves. Marijuana & Analgesia.
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Society for Neuroscience in New Orleans, LA, USA. www.omma1998.org/analgesia_mj.htm
5 Walker, Huang, Strangman,Tsou, & Sanudo-Pena: “Pain modulation
by release of the endogenous cannabinoid anandamide”. Proceeding
of the National Academy of Sciences: October 12, 1999.
6 GW Pharmaceuticals Research and Development on pain: www.gwpharm.com/research_pain.asp
7 GW Pharmaceuticals Press Release: www.gwpharm.com/
8 International Association for Cannabis as Medicine: www.acmed.org/english/nav/home-science.htm
9 J Joy, S Watson, J Benson. Editors of Marijuana and Medicine: Assessing
the Science Base. Institute of Medicine. 1999. Page 145 of hardback
edition. www.nap.edu/catalog/6376.html
10 ORS 475.300 — ORS 475.346 www.dhs.state.or.us/publichealth/mm/475a.cfm#300
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14 Marinol( brand of dronabinol (THC) manufacturer’s package
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30 Grotenhermen, Franjo, Gero Leson, Günter Berghaus, Olaf Drummer,
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(ICADTS): August 10th, 2004, Glasgow, Scotland
