Wednesday, November 08, 2006



So you say your 15 year old doesn’t pay attention in school, he fidgets in class, is sometimes disruptive and is just barely getting by grade wise. But wait. Recently he’s been doing a lot better. He’s keeping up with his homework and his grades have gone from C minuses to As and Bs. Then all of a sudden he’s back to his old tricks, busted at school for marijuana.

Maybe we need to take a closer look and see if there really is something more significant going on. Maybe, just maybe, the scientists who are studying the endocannabinoid system and clinicians treating patients with cannabis, cannabinoids and anandamide blockers are right and he really is treating his ADHD. Your first reaction is to dismiss that idea. But read on and you won’t be so quick to be influenced by 90 years of unscientific propaganda.

ADHD is a costly problem that strains medical/mental health, educational, and legal institutions[1]. ADHD afflicts 3-5% of Americans [2]. It is one of the most common psychiatric disorders of childhood[3] and in adults frequently results in tragic consequences in professional and personal lives[4]. ADHD is characterized by persistent impairments in attention (or concentration) and/or symptoms of hyperactivity and impulsivity[5].

The preponderance of studies show marijuana use is overwhelmingly prevalent with ADHD sufferers, either as a self-medicament or for recreation[6]. While some apply preconceptions that marijuana exacerbates ADHD almost all California cannabinologists believe camnabis and cannabinoids have substantially improved the lives of ADHD sufferers, and with less negative side effects than common stimulant drug ADHD treatments.

As we have come to understand more about the brain and the role of dopamine and the endocannabinoid system we are starting to unravel how cannabis, anandamide and dranabinol act to free up dopamine and decrease the overstimulation of the midbrain. But before we jump to the present we need to recognize that ADHD sufferers react differently to stimulant drugs from the average population[7]. This was first noted in 1937 when Dr. Charles Bradley attempted to treat the first recognized cases of ADHD.(ADHD has gone by the names of Minimal Brain Dysfunction [MBD], hyperkinesis, etc.) After trying sedatives his patients became more hyperactive. Noting this paradox he tried amphetamines¾which calmed them down.

From that point, stimulants (sympathomimetic drugs) became the mainstay for treating ADHD. It turns out that they work by tying up dopamine transporter thus freeing up dopamine, previously bound to the dopamine transporter, to engage in retrograde inhibition. Dopamine is essentially acting as a damper on neurotransmission by depolarizing the neuron that just released it. The stimulants main draw back is that they come with a host of unacceptable side effects-jitteriness, anxiety, sleep difficulty, appetite suppression and a propensity to be quick to anger.

It turns out that cannabis also frees up dopamine but it has a very benign side effect profile. Noting cannabis’ vastly superior side effect profile DEA Administrative Law Judge, Francis L. Young, after a two-year hearing to reschedule cannabis in 1998 said:

"Nearly all medicines have toxic, potentially lethal effects. But marijuana is not such a substance. There is no record in the extensive medical literature describing a proven, documented cannabis-induced fatality .... In strict medical terms marijuana is far safer than many foods we commonly consume ... Marijuana, in its natural form, is one of the safest therapeutically active substances known to man."

The results in treating ADHD with cannabis are often spectacular .Patients report grades going from Cs and Ds to As and Bs. Dr. David Bearman, a physician practicing in Santa Barbara California, reports patients have said “I graduated from the Maritime Academy because I smoked marijuana”, and “I got my Ph. D because of smoking marijuana.” Almost universally ADHD patients who therapeutically used cannabis reported it helped them pay attention in lecture, focus their attention instead of thinking of several ideas almost at the same time, helped them to stay on task and do their homework.

Marijuana Science & the Brain

In the 1940s tetrahydrocannabinol (THC) was identified as the major psychoactive in marijuana.In 1964 Israeli scientist Rapheal Mechulam, isolated the most pharmacologically active of the 483 chemical in cannabis,delta 9 THC. While the psychoactive effects of marijuana are still mostly attributed to THC[8] several cannabinoids, flavinoids and terpenoids also from cannabis, are thought to have therapeutic value.

In the 1990s, scientists discovered vast amounts of THC receptors in the mammalian (e.g., cows, dolphins, humans) central nervous system. This system is now known as the endocannabinoid system and is a major part of the human brain. Its importance was accepted when it was learned that THC receptors exist in greater numbers than receptors for hundreds of drugs used in modern medicine[9]. This initiated widespread medical interest in marijuana; new findings appear almost daily in the medical literature[10].

The first cannabinoid-receptors in the human brain were named CB1 and CB2. They are located in high concentration in the midbrain in the limbic system and in the forebrain of the cerebral cortex. Soon it was found that the human brain produces over 60 endocannabinoids (i.e., THC-like substances)[11]. Endocannabinoids exert most of their pharmacological actions by activating the CB1 receptor in the brain[12]. While the brain produces its own cannabinoids, smoking marijuana also stimulates the body's endocannabinoid system.

70% of the brain's job is to inhibit sensory input from the other 30%

Typical ADHD symptoms include distractibility. The most accepted theory about ADHD rests on the fact that about 70% of the brain’s function is to regulate input to the other 30% (ADHD page). The cause of ADHD is probably a decreased ability to suppress sensory input both internal and external input (need a reference here).Basically the brain is overwhelmed with to much information come to fast. In ADHD the brain is cluttered with and too aware of all the nuances of a person’s daily experience. This phenomenon is caused by a dopamine dysfunction.

Dopamine (a neurotransmitter in the brain) is a key suppressor of stimuli to the brain.It works by a unique mechanism, retrograde inhibition. By the dopamine depolarizing the neuron that just released it, that neuron becomes more difficult to stimulate and the speed and frequency of neural firing in that part of the brain is decreased. Without dopamine, we cannot distinguish or maybe we should say, focus and concentrate on what is important information (a boss giving us important instructions) from not so important information (e.g., daydreams). Persons with ADHD have significant irregularities in their dopamine management systems[13]

In the late 1990’s, researchers discovered how Ritalin®, the popular ADHD treatment, works¾it increases dopamine levels[14]. The story would have ended there if Ritalin did not have significant potential to cause permanent brain damage and psychiatric problems[15],[16]. (Bill this seems way too strong) Even non-stimulant ADHD drugs have serious psychiatric problems[17].

Since the endocannabinoid system was discovered, many studies revealed that marijuana also modulates the dopamine system[18] and therefore is a potential ADHD treatment. As recounted in the physicians’ stories below, marijuana may a safer, less costly, and more effective treatment than anything available from the pharmaceutical companies.

Doctors Speak Up

Dr. Claudia Jensen

Dr. Claudia Jensen, a 49-year old California pediatrician and mother of 2 teenage daughters, says marijuana might be the best treatment for ADHD[19]. In a recent interview with the FOX news network, she said:

"Why would anyone want to give their child an expensive pill…with unacceptable side effects, when he or she could just go into the backyard, pick a few leaves off a plant and make tea…?"

"Cannabinoids are a very viable alternative to treating adolescents with ADD and ADHD…I have a lot of adult patients who swear by it."

In her testimony, befor the House Committee on Government Reform on Marijuana (2004) Dr. Jensen discussed the practice of recommending marijuana to patients with ADHD[20] in an 11-page statement. Her testimony summarized hundreds of published scientific articles on the safety/ efficacy of marijuana that have produced strong scientific evidence that marijuana is important medicine.

Her reasons for looking to marijuana as treatment for ADHD?

“The other legal drugs used to treat ADD are helpful in many patients, but they all have side effects….the other five of the nine drugs used to treat ADD in this country haven’t even been scientifically tested…for ADD in children. These are drugs for depression and high blood pressure…Of all the drugs used to treat ADD, cannabis has the least number of serious side effects.

Her explanation for why marijuana is opposed by the pharmaceutical companies:

“The real problem with allowing patients to use Cannabis as a medication is economics…If Cannabis were approved for use in just the ADD/ ADHD market alone, it could significantly impact the $1 Billion a year sales for traditional ADD/ ADHD pharmaceuticals…”

Dr. Tom O'Connell

Dr. Tom O'Connell, a retired surgeon who works with patients in the Bay Area is studying with patients that self-medicate with marijuana. In O’Shaughnessy’s, The Journal of Cannabis in Clinical Practice (Spring 2005) Dr. O'Connell summarized his study of 790 patients:

“…There is universal agreement among applicants who have been diagnosed with and/or treated for ADD that cannabis helps them achieve and retain focus…”

Dr. O’Connell states there is a strong argument for promoting marijuana with ADHD because it is safer than all other medications. In 2004 a statement to Fox news, he said:

“…Although it flies in the face of conventional wisdom, it's nevertheless true that cannabis is far safer and more effective than the prescription agents currently advocated for treatment of ADD-ADHD…”

Is Marijuana Safe?

The preponderance of scientific evidence points to marijuana as being exceptionally safe, for adolescents and adults. Leo Holllister’s two papers Health Aspects of Cannabis (1986) and Health aspects of cannabis: revisited (1998) are widely considered the most authoritative compendia on the safety of marijuana[21]. Hollister’s opinion is best summarized in his 1986 paper:

“…one is forced to conclude that cannabis is relatively safe…toxicity studies of cannabis and its constituents lead to the inescapable conclusion that it is one of the safest drugs ever studied in this way.”[22]

In the many papers that cite Hollister’s work, there is a common theme:

“By any standards, THC must be considered a very safe drug both acutely and on long-term exposure.”[23]

“…although there have been many rumors that the long term use of marijuana leads to irreversible damage to higher brain functions the results of numerous scientific studies have failed to confirm this…Based on the results of the three best studies performed (Schwartz, Pope and Block et al.,) residual cognitive effects are seldom observed and if present are mild in nature.” [24]

FDA Administrative Law Judge Young couldn’t have been clearer in describing the safety of cannabis. He said after a two year FDA rescheduling hearing, that marijuana was one of the safest therapeutic agents known to man. According to ALJ Young marijuana is safer than eating 10 potatoes. His recommendation to reschedule marijuana to schedule II was turned down by President Bushes’ political appointee, FDA Director John Lawn


With the discovery of cannabinoid receptors and a greater understanding of the endocanabinoid system we stand at the dawn of a new era of understanding how the brain works and applying new solutions. This is a time to look at not only creating new agonists and antagonists based on the cannabinoid molecule but also to recognize the medicinal role that cannabis can play not only in treating ADHD but also possibly seizures, Tourette’s Syndrome, PTSD,OCD and panic attacks. We in the US need to reevaluate our attitude regarding phytochemicals.

There is a contemporary movement that physicians practice evidence based medicine. That is much easier said then done. As the recent Vioxx ® example demonstrates FDA approval does not guarantee that serious side effects won’t be discovered after a studied and FDA approved drug is used by tens of millions, rather than a few thousand test subjects. We need to adopt some of the European respect for the value of hundreds and in some cases (as is the case with cannabis) years of human experience with herbal and natural preparations as some sort of evidence. In some instances these traditional remedies, sometimes ridiculed, have fewer side effects and work as well or better than FDA approved , single chemical drugs.

Let’s face it, not all so called research is done by the federal or state government. Most clinical studies are done by drug companies and they are not an unbiased third party. We most rely on the expertise and over site of the FDA to sort the wheat from the chaff. They must pay attention to the science and methodology of the studies submitted. If possible they should have access to the studies which weren’t submitted to them since pharmaceutical companies have been known to provide biased research, rooted in financial conflict and preconceived notions. [25]. [26]. Costly proprietary drugs are heavily promoted but herbal remedies, which cost the patient relatively little, have at least until recently, been given relatively short shrift by the medical establishment.

Six years ago the CMA, at their annual leadership conference, urged physicians to be aware of their patients’ use of complementary and alternative medicines (CAM). Over 60 % of the average doctors patients use CAM, however at least 40% do not share that fact with their physician. One of those herbs [patients use is cannabis and one of the conditions patients have found it’s useful for is treating ADHD.

Physicians, judges, and researchers are beginning to acknowledge the medical value of cannabis. In the case of treatment for ADHD cannabis and cannabinoids are often an effective, safer alternative then sympathomimetic prescription drugs. These stimulant drugs have an unacceptable side effect profile.

If you want to talk about marijuana, choose a physician that has experience with marijuana. More and more physicians are becoming aware of cannabis medicinal value. UCSD is headquarters for the California Marijuana Research Center. They administer 18 FDA approved smoked cannabis medical clinical studies. These studies are showing good results and being presented at medical meetings. Bayer is marketing tincture of cannabis in Canada under the trade name Sativex .The International Cannabis Research Society has annual meetings discussing progress being made in how cannabis works what almost seems like its magic.

[1] Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder. NIH Consensus Statement Online 1998 Nov 16-18; 16(2): 1-37.

[2] National Institutes of Health Consensus Development Conference Statement. Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD). Journal of the American Academy of Child and Adolescent Psychiatry, 2000; 39(2): 182-93.

[3] American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Text Revision), Washington, DC: APA.

[4] Murphy K. Psychosocial Treatments for Adhd in Teens and Adults: a Practice-Friendly Review. J Clin Psychol. 2005; 61(5):607-19.

[5] Kutcher S. et al. International Consensus Statement on Attention-Deficit/Hyperactivity Disorder (Adhd) and Disruptive Behaviour Disorders (Dbds): Clinical Implications and Treatment Practice Suggestions. Eur Neuropsychopharmacol. 2004; 14(1):11-28.

[6] Dodson Ww. Pharmacotherapy of Adult Adhd. J Clin Psychol. 2005; 61(5):589-606.

[7] Dodson Ww. Pharmacotherapy of Adult Adhd. J Clin Psychol. 2005; 61(5):589-606.

[8] Pertwee Rg. The Central Neuropharmacology of Psychotropic Cannabinoids. Pharmacol Ther. 1988; 36(2-3):189-261.

[9] Herkenham M et. al. Cannabinoid Receptor Localization in Brain [Journal Article]. Proc Natl Acad Sci U S A. 1990; 87(5):1932-6.

[10] De Petrocellis L et. al. The Endocannabinoid System: a General View and Latest Additions [Journal Article]. Br J Pharmacol. 2004; 141(5):765-74.

[11] Murillo-Rodriguez Eric, et. al. Anandamide Modulates Sleep and Memory in Rats. Brain Research. 1998; 812(1-2):270-274.

[12] Pertwee Rg. Pharmacology of Cannabinoid Cb1 and Cb2 Receptors. Pharmacol Ther. 1997; 74(2):129-80.

[13] Oades, et. al., Dev Sci. 2005 Mar;8(2):122-31.

[14] Nora D. Volkow et. al. The Journal of Neuroscience 2001;21:RC121.

[15] Moll GH et. al. J Child Adolesc Psychopharmacol 2001 Spring;11(1):15-24

[16] William Carlezon et. al. Biol Psychiatry. 2003 Dec 15;54(12):1330-7.

[17] Food and Drug Administration. Public Health Advisory Suicidal Thinking in Children and Adolescents Being Treated With Strattera (Atomoxetine). 29 September 2005.

[18] Rodriguez De Fonseca F et. al. Role of the Endogenous Cannabinoid System as a Modulator of Dopamine Transmission: Implications for Parkinson's Disease and Schizophrenia. Neurotox Res. 2001; 3(1):23-35.



[21] Mechoulam R and Golan D. Comment on 'health Aspects of Cannabis: Revisited'. Int J Neuropsychopharmcol. 1998; 1(1):83-85.

[22] Hollister Le. Health Aspects of Cannabis. Pharmacol Rev. 1986; 38(1):1-20.

[23] Iversen, Leslie L. The science of marijuana, p. 181. Oxford University Press, 2000.

[24] Iversen, Leslie L. The science of marijuana, p. 97. Oxford University Press, 2000.

[25] John P. A. Ioannidis. Why Most Published Research Findings Are False. PLoS Med. 2005 August; 2(8): e124.

[26] John P. A. Ioannidis, MD. Contradicted and Initially Stronger Effects in Highly Cited Clinical Research. JAMA. 2005; 294:218-228.