Autism Marijuana Treatment Research

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Autism Marijuana Treatment Research

 

Charlotte’s Web is a high-cannabidiol (CBD), low-tetrahydrocannabinol (THC) Cannabis extract marketed as a dietary supplement under federal law of the United States.[1][2][3] It is produced by the Stanley brothers in Colorado. It does not induce the psychoactive “high” typically associated with recreational marijuana strains that are high in THC.[4] In September 2014, the Stanleys announced that they would ensure that the product consistently contained less than 0.3% THC.[5]

Charlotte’s Web is named after Charlotte Figi, born October 18, 2006 (age 11), whose story has led to her being described as “the girl who is changing medical marijuana laws across America.”[6] Her parents and physicians say she experienced a reduction of her epileptic seizures brought on by Dravet syndrome after her first dose of medical marijuana at five years of age. Her usage of Charlotte’s Web was first featured in the 2013 CNN documentary “Weed”. Media coverage increased demand for Charlotte’s Web and similar products high in CBD, which has been used to treat epilepsy in toddlers and children. It was originally called “Hippie’s Disappointment” as it was a strain that had high CBD instead of THC.[7]

While anecdotal reports have sparked interest in treatment with cannabinoids,[8] there is not enough evidence to draw conclusions about their safety or efficacy.[8][9] Physicians worry that some parents are willing to try treatments before proper research has been conducted, and that they may be disappointed. They are “alarmed by parallels to past miracle-cure manias later proved false…” and “…wary of the heightened placebo effect in treatments involving children, when reports of progress depend on the view of parents.”[10]

Medical uses[edit]

Evidence[edit]

There is little evidence about the safety or efficacy of cannabinoids in the treatment of epilepsy.[8][11] A 2014 Cochrane review did not find enough evidence to draw conclusions about its use.[12]A 2014 review by the American Academy of Neurology similarly concluded that “data are insufficient to support or refute the efficacy of cannabinoids for reducing seizure frequency.”[13]

The Cochrane review suggests cannabinoids be reserved for people with symptoms that are not controllable by other means, who have been evaluated by EEG-video monitoring to confirm diagnosis, and are not eligible for better established treatments such as surgery and neurostimulation.[14] A second review described four placebo-controlled trials of cannabadiol including 48 people with a disease that was not manageable by other means. Three out of four trials reported some reduction in seizures, but no comparison with placebo was possible due to the small number of people in the trials. The drugs were well tolerated.[15] A third review found that no reliable conclusions about the effect of cannabis on epilepsy could be drawn due to the poor quality of available data, but further research may be warranted because of the good safety profile observed in small clinical trials.[16]

A 2017 study found cannabidiol reduced convulsive seizures but resulted in more side effects in people with Dravet syndrome.[17]

Statements[edit]

Due to the anecdotal nature of the health claims being made medical bodies have published statements of concern.

A position statement by the American Epilepsy Society states:

The recent anecdotal reports of positive effects of the marijuana derivative cannabidiol for some individuals with treatment-resistant epilepsy give reason for hope. However, we must remember that these are only anecdotal reports, and robust scientific evidence for the use of marijuana is lacking… at present, the epilepsy community does not know if marijuana is a safe and effective treatment, nor do they know the long-term effects that marijuana will have on learning, memory and behavior, especially in infants and young children.[18]

Cannabis-derived products are not mentioned in the National Institute for Health and Care Excellence epilepsy treatment guidelines.[19]

History[edit]

 

Cannabis oil

Charlotte’s Web was developed in 2011 by the Stanley brothers (Joel, Jesse, Jon, Jordan, Jared and Josh[20]) through crossbreeding a strain of marijuana with industrial hemp.[21] This process created a variety with less tetrahydrocannabinol (THC) and more cannabidiol (CBD) than typical varieties of marijuana.[22] The variety shows potential for medical usage, especially for those who do not wish to experience the typical high of recreational marijuana use.[23] As it is so low in THC, the variety was originally called “Hippie’s Disappointment”,[24] and also has been labeled “boring”.[25] It is a less profitable plant[26] with “close to no value to traditional marijuana consumers.”[27]

The Stanley brothers grow the plants at their farm and greenhouses. A CBD rich oil is extracted from the harvested plants and concentrated through rotary evaporation.[28] To make it easier to perform clinical trials, they are planning to move the Charlotte’s Web part of their operation to Uruguay. By doing so, they will also be able to import it into any U.S. state as hemp.[2][3]

The Realm of Caring Foundation (RoC),[1] a 501(c)(3) nonprofit organization,[29] was set up by the Stanley brothers to help patients “who can’t afford the treatment.”[24] They have also started “Stanley Brothers Social Enterprises, Inc.”,[3][30][31] which has registered the trademark “Charlotte’s Web Hemp Products”.[32] Some products are marketed through CW Hemp (formerly CW Botanicals).[33]

Society and culture[edit]

Legal status[edit]

With the main ingredient being classified as “industrial hemp”, (Farm Bill) Charlotte’s Web Oil and other CBD products are legal in all 50 states; (as long as the THC content is <0.3%) as they are dietary supplements.[citation needed]

The publicity associated with Charlotte’s Web has inspired a number of legislative bills, some of which are in the planning stages, and others which have been proposed or actually passed. Children, as “uniquely powerful advocates for medicinal pot across the country,”[34] have inspired “the movement to legalize medicinal marijuana,” a movement which “has a face like Charlotte’s–and it’s a young one that’s hard to ignore. Lawmakers across the country are pushing legislation to legalize marijuana oil as a treatment for children with epilepsy.”[35]

Colorado law permits the use of medical cannabis for eight conditions: cancerglaucomaHIV/AIDS, muscle spasms, seizures, severe pain, severe nausea and dramatic weight loss, and muscle atrophy.[22] The publicity surrounding anecdotal reports of successful treatment of intractable epilepsy with cannabinoids is likely to lead to a surge in interest.[8]

In 2013, the parents of a two-year-old with Dravet syndrome confronted New Jersey governor Chris Christie, who signed a bill allowing access for sick children to medical marijuana[27] in a controversy dubbed “pot for tots”.[27][36][37]

In 2014, legislative proposals in Utah,[38][39] Arizona,[40] New York,[41] Washington state,[27] Minnesota,[42] and Florida[43][44] were considered, where “even some staunch opponents of medical marijuana now are willing to make an exception” to allow the marijuana extract for medical treatment.[4]

In Utah, Rep. Gage Froerer, R-Huntsville, said in October 2013: “Nothing in federal or state law prohibits the sale or use of hemp products.”[28] He pledged to consult with the Utah Substance Abuse Authority, saying: “We need to take a strong look at this and make sure that we as a legislature and we as citizens understand really what this is and what it’s not.”[45] In November 2013, he said he would address “three components in sponsoring legislation: access, quality control and research. He said the Utah Department of Health would probably be involved in quality-control efforts…”[46] Annette Maughan, President of the Epilepsy Association of Utah, said: “The current Utah law doesn’t exclude its use but also doesn’t allow for its use. We are in limbo until Utah lawmakers decide what to call it.”[45] On March 21, 2014, Gary Herbert, the governor of Utah, signed a bill giving “families access to the marijuana extract for treating epilepsy.”[40] The state bill, HB0105, allows import of Charlotte’s Web extract across state lines from Colorado to Utah, and covers only use for intractable epilepsy with the consent of a neurologist.[38][39] Also on March 21, 2014, an Arizona court found “that Arizona’s medical marijuana law allows consumption of the plant in extract form.”[40]

On March 20, 2014, the Florida House of Representatives Budget Committee passed the “so-called Charlotte’s Web measure (CS/HB 843)”[44] designed to limit prosecutors’ ability to prosecute those in possession of low THC/high CBD marijuana (“0.5 percent or less of tetrahydrocannabinol and more than 15 percent of cannabidiol”) used for treating seizures. The law took effect July 1, 2014.[47][48] Since then, Florida legislators have passed a bill with bipartisan support legalizing the use of Charlotte’s Web,[49] and Governor Rick Scott signed the “Compassionate Medical Cannabis Act of 2014” (SB 1030)[43][50] into law on June 6, 2014. The law is also referred to as the “Charlotte’s Web” law.[51][52] The law specifies the number of distribution centers, which types of nurseries can grow the plants, requires various other controls,[53] and provides funding for research.[43]

On October 31, 2017, the FDA sent warning letters to four CBD marketers, including Stanley Brothers Social Enterprises, LLC (d/b/a CW Hemp), the producer of Charlotte’s Web. They were warned “against making medical claims about cannabidiol (CBD). The agency also took issue with the businesses marketing CBD products as dietary supplements”.[61]

Reactions to CBD-only laws[edit]

The federal Schedule 1 drug classification[62] blocks broad scientific research on cannabis. However, in late 2015, the United States Drug Enforcement Administration (DEA) eased some regulatory requirements imposed by the Controlled Substances Act (CSA) for those who are conducting FDA-approved clinical trials on cannabidiol (CBD). These modifications will streamline the research process regarding CBD’s possible medicinal value and help foster ongoing scientific studies.[63]

But the Marijuana Policy Project has expressed frustration over the fact that many legislative efforts inspired by Charlotte’s Web are aimed at only legalizing low or no THC, high CBD medical marijuana products. They believe that such legislation is too restrictive and ignores claimed benefits of THC, leaving “behind around 98% of the individuals who can benefit from it.”[64] Referring to the “Charlotte’s Web Medical Hemp Act of 2014”, an editorial in Ladybud Magazine expressed concern that the law “leaves thousands of patients out in the cold without safe, legal access to medical cannabis. It also ignores science that seems to indicate that whole plant medicine is optimal.”[65]

Name[edit]

Charlotte’s Web is named after an American girl, Charlotte Figi. She developed Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI) as a baby. By age three, Figi was severely disabled and having 300 grand mal seizures a week despite treatment.[22][66] Her parents learned about another child with Dravet Syndrome, who had been using a different type of medical marijuana since June 2011, and decided to try marijuana.[67] Her parents and physicians said that she improved immediately. She now follows a regular regimen that uses a solution of the high-CBD marijuana extract in olive oil. She is given the oil under her tongue or in her food.[22][68] Her parents said in 2013 that her epilepsy had improved so that she had only about four seizures per month, and she was able to engage in normal childhood activities.[22][69]

The type now named after Figi was not the first type her parents tried. As their original supply, a type called R4 that is also high in CBD and low in THC, was running out, they contacted the Stanley brothers. From the Stanleys’ stock, they chose the high-CBD variety that has since been renamed to Charlotte’s Web.[22]

Charlotte’s story has been featured on two CNN documentaries,[23][26] The Doctors TV show,[70] 60 Minutes Australia,[71] and Dateline NBC,[72] among many other sources. An article in the National Journal detailing the role of several children as “uniquely powerful advocates for medicinal pot across the country” described Charlotte as the “first poster child for the issue….”[34] Her story has led to her being described as “the girl who is changing medical marijuana laws across America,”[6] as well as the “most famous example of medicinal hemp use”.[73]

Publicity and demand[edit]

When Charlotte was five years old, her story was featured in the August 11, 2013 CNN documentary “Weed”, hosted by Sanjay Gupta.[23] On November 24, 2013, Paige Figi was a guest on The Doctors TV show, where Charlotte’s story was told.[70] She was also featured in Gupta’s March 11, 2014 CNN documentary “Weed 2: Cannabis Madness”.[26] The extract received more publicity on October 6, 2014, when The Doctors TV show again featured a story about usage of Charlotte’s Web. The physicians called for a change of the Federal classification.[74] Sanjay Gupta has also expressed his support for Charlotte’s Web on The Doctors TV show.[75] On the October 17, 2014 episode of the ABC TV series The View, Paige Figi and Joel Stanley were interviewed by Whoopi Goldberg and Nicolle Wallace.[66]

The CNN documentaries received widespread publicity and popularized Charlotte’s Web as a possible treatment for epilepsy and other conditions.[22] Colorado has legalized both the medicinaland recreational use of marijuana, and many parents have flocked there with their suffering children in search of Charlotte’s Web and other forms of medical marijuana.[76] In November 2013, CBS Denver reported that “[t]here is now a growing community of 93 families with epileptic children using marijuana daily. Hundreds are on a waiting list and thousands are calling.”[24] In October 2014, Time noted the Stanley brothers had a waiting list of “more than 12,000 families.”[77] They have been termed “marijuana refugees”,[24] “part of a migration of families uprooting their lives and moving to Colorado, where the medicinal use of marijuana is permitted…forced to flee states where cannabis is off limits.”[78][79] In November 2014, David Nutt mentioned Charlotte’s Web in the Royal Pharmaceutical Society‘s Pharmaceutical Journal, where he appealed for “the UK government [to] acts on evidence, allowing the use of medicinal cannabis and reducing barriers to its research.”[80]

Families who say they have run out of pharmaceutical options have moved to Colorado to access Charlotte’s Web. The demand has spurred calls for more research to determine whether these products actually do what is claimed. Amy Brooks-Kayal, vice president of the American Epilepsy Society, stated that epileptic seizures may come and go without any obvious explanation, and that Charlotte’s web could cause developmental harm. She recommended that parents relocate so that their affected children could have access to one of the nation’s top pediatric epilepsy centers rather than move to Colorado.[81]

The product has been described as the “country’s most famous brand of CBD oil”,[82] the “largest selling CBD oil in the country”,[83] and the “number one brand”, with 7% of the market.[84]

Distribution[edit]

In November 2013, Josh Stanley said that Charlotte’s web was 0.5% THC and 17% CBD,[20] and that it “is as legal as other hemp products already sold in stores across Utah, including other oils, clothing and hand creams, but is illegal, federally, to take across state lines.”[85] The legalities of selling the product to people who transport it across state lines is complicated, with difficulties for both the sellers and transporters. Regardless of state laws in Colorado and Utah which would allow the practice, it is still a Federal offense to transport hemp products across state lines.[86][87] In September 2014, the content was measured at 0.3% THC.[5]

Research[edit]

The relationship between the Schedule I status of cannabis in the United States and the lack of scientific research on cannabis has been claimed by some to be directly related.[88] The situation has been described as a “catch-22” paradox: “Marijuana is restricted in large part because there is little research to support medical uses; research is difficult to conduct because of tight restrictions.”[89] Sanjay Gupta has described the complex interaction between restrictive laws and lack of scientific research:

Gupta repeated throughout the evening that the “policy has outpaced the science.” The states, he said, “are moving forward without waiting for the science, and the issue is only compounded by the fact that the ‘policies and the laws we have in [the US] make it challenging for the science to get done.”[88]

Even though the Florida “Compassionate Medical Cannabis Act of 2014” (SB 1030)[43] provides funding for research, the status of all cannabis products as illegal Schedule I drugs has limited the amount of research, with the University of Florida refusing to do such research for fear of losing federal funding.[51][90]

The interest created by the documentary highlighted a need for increased scientific research, as well as caution against “bad medicine” and raising false hopes: Ed Maa, a specialist in epilepsy, stated: “This is not going away. …I think it needs to be studied vigorously and very quickly.” He hopes to “launch a clinical trial to study the pot and its potential.”[24] Physicians have called for more research to better understand the potential benefits of controlled use of medical marijuana;[8] Sharon Levy, director of the Adolescent Substance Abuse Program at Children’s Hospital Boston said:

“The AAP strongly supports more cannabinoid research to better understand both how these substances can be used therapeutically as well as their potential side effects—which we may well be underestimating…[But] the AAP does not support ‘medical marijuana’ laws as they circumvent regulations put in place to protect patients, and children are a particularly vulnerable population.”[8]

Physicians have expressed both positive interest and worry about the sudden explosion of interest in the legalization of medical marijuana and its research, admitting legalization is both “a scientist’s dream or a doctor’s nightmare.” They fear that some parents are too open to trying anything before proper research has been conducted, and that they may be disappointed. They are “alarmed by parallels to past miracle-cure manias later proved false…” and “…wary of the heightened placebo effect in treatments involving children, when reports of progress depend on the view of parents.”[10] There is also danger that “the [legalization] movement also opens the way for bad medicine…through treatments at best giving hope to the hysterical and at worst delivering damaging side effects.”[10] According to Alan Shackelford, Charlotte Figi’s physician: “We really don’t know how it works… The cannabidiol seems to act as a neuro-stabilizer, but how? The research is minuscule on this.”[91]

Orrin Devinsky, a neurologist at New York University’s Comprehensive Epilepsy Center, where he will conduct clinical trials on Epidiolex,[92] a high-CBD drug from GW Pharmaceuticals, expressed his sympathy for those who do not want to wait for research results:[4]

I had a child who had failed 15 medications and drug treatments and there was nothing else to do, and they were having many seizures a day that were terribly disabling, I think it would be a very reasonable thing to do to try a high-CBD cannabis product.

He also expressed concern that the number of parents using the Charlotte’s Web extract will make it harder to find children for the clinical trials, and that:

There are many more unknowns than knowns…the focus of the community—lay and scientific and governmental—should be on getting good information. That should be the real focus of what we need right now.[4]

The Epilepsy Foundation and Devinsky issued a joint statement calling for increased research and immediate access to medical marijuana, specifically naming Charlotte Figi’s case. Devinsky said:

We need to make a balanced decision about compassionate use. If I were Charlotte Figi’s parents and lived in Colorado I would have done exactly what they did. And as a doctor, I would gladly prescribe marijuana products for many of my patients who failed existing therapies if it were legal in my state. … Until we have the scientific data, we should make medical marijuana available to physicians who care for people with treatment-resistant epilepsy and their patients.[93]

Due to reports that some people with Dravet syndrome seem to benefit from treatment with Charlotte’s Web, an observational clinical trial was launched in September 2014 at the University of Colorado.[94] The study will run until February 2016, will focus on genetic differences between people who respond and do not respond, and attempt to determine if such genetic factors may be related to the success or failure of treatment.[95]

In January 2018, it was reported that trials with Epidiolex, a high-CBD pharmaceutical, had been successful enough that it might be “available as soon as the second half of 2018 in the United States, pending Food and Drug Administration approval.”[96]

O’Shaughnessy’s • Summer 2010
Autism is one of a group of conditions known as
pervasive developmental disorders. This mysterious
disability, first described and named more than 60 years
ago, is characterized by striking emotional and cognitive
isolation and detachment.
Autistic children are characterized by their apparent
inability to form human relationships, abnormal or
absent speech, and an unusually limited range of activities
and interests. It is estimated that three to six out of
every 1000 children in the United States has autism,
about three quarters of them are boys, and the number
of cases appears to be rising. It is not clear whether
this is due to better detection and reporting of autism,
a real increase in the prevalence, or both.
While symptoms of autism often occur in the first
months of life, they may be disregarded at first, but
by the age of two or three it is clear that something is
seriously wrong. Autistic children show little interest
in others, children or adults. They do not communicate
experiences and there is little if any spontaneous or
imaginative play; instead they prefer monotonous,
solitary activities. They may spend hours performing
ritualistic repetitive motions. They can be fascinated
by one limited subject or activity to the exclusion of all
others and they are sometimes violent in their resistance
to efforts to change the focus of their attention. They
appear to fear novelty and may explode in rage when
faced with change.
Many autistic children are hypersensitive to minor
noises, smells and physical sensations, and some are
hyperactive, impulsive, aggressive and self-destructive.
They may throw tantrums in response to apparently
trivial frustration, repeatedly bite themselves, hit themselves
with their fists, or strike their heads against a
wall. Their language develops slowly and in an odd
way, making them unintelligible; some do not speak
at all. The vast majority, but not all, are retarded. A
few, who may or may not be retarded, have unusual
talents; they are known as savants.
There is no cure for autism, nor is there “one-sizefits-all”
treatment. Treatment options include behavior
and communication therapies, educational therapies
and drug therapies. Our interest here is in exploring
the possibility of a new drug therapy.
Drugs have a place in treating autistic symptoms, but
their uses are limited. Antipsychotic drugs and mood
stabilizers may help autistic patients who repeatedly
injure themselves. The older conventional antipsychotic
drugs have serious side effects on body movements.
The novel or atypical drug risperidone (Risperdal) has
shown a glimmer of promise in recent research. Anticonvulsants
may be useful in suppressing explosive
rage and calming severe anxiety. About 20% of autistic
people have epileptic seizures, and some researchers
have suggested that unrecognized partial complex
seizures, which cause changes in consciousness but
not muscular convulsions, are one source of autistic
behavior disturbances.
In several studies, selective serotonin reuptake inhibitors
(SSRIs) have been found to relieve depression
and anxiety and reduce compulsive ordering, collectA
Novel Approach to the Symptomatic Treatment of Autism
by Lester Grinspoon M.D.
ing, and arranging. Unfortunately, little is known about
the long-term effects of drugs in autistic children, and
no known drug has any effect on the underlying lack
of capacity for empathy and communication.
A Mother’s Report
With the explosive growth of interest in exploring
the medicinal capacities of marijuana, some courageous
parents, concerned about the toxicity of the
above-mentioned drugs, and desperate to find pharmaceutical
means of relieving their children of some of the
harsh symptoms of autism, have been experimenting
with oral doses of cannabis. The following anecdote
was provided by Marie Myung-Ok Lee who teaches
at Brown University. She is the author of the novel
Somebody’s Daughter and is a winner of the Richard
Margolis award for social justice reporting.
“My son J, who is nine years old, has autism. He’s
also had two serious surgeries for a spinal cord tumor
and has an inflammatory bowel condition, all of which
may be causing him pain, if he could tell us. He can say
words, but many of them don’t convey what he means.
“J’s school called my husband and me in for a meeting
about J’s tantrums, which were affecting his ability
to learn. Their solution was to hand us a list of child
psychiatrists. Since autistic children like J can’t exactly
do talk therapy, this meant sedating, antipsychotic drugs
like Risperdal (risperidone).
“As a health writer and blogger, I was intrigued
when a homeopath suggested medical marijuana. Cannabis
has long-documented effects as an analgesic and
an anxiety modulator. Best of all, it is safe. A publication
by the Autism Research Institute described cases
of reduced aggression, with no permanent side effects.
“After a week on Marinol, which contains a synthetic
cannabinoid, J began garnering a few glowing
school reports. But J tends to build tolerance to synthetics,
and in a few months, we could see the aggressive
behavior coming back. One night, at a medicalmarijuana
patient advocacy group, I learned that the
one cannabinoid in Marinol cannot compare to the 60
in marijuana the plant.
“Rhode Island, where we live, is one of 14 states
where the use of medical marijuana is legal. And yet,
I hesitated. Now we were dealing with an illegal drug,
one for which few evidence-based scientific studies
existed precisely because it is an illegal drug. But when
I sent J’s doctor the physician’s form that is mandatory
for medical marijuana licensing, it came back signed.
We underwent a background check, and J became the
state’s youngest licensee.
“The coordinator of our medical marijuana patient
advocacy group introduced us to a licensed grower,
who had figured out how to cultivate marijuana using
a custom organic soil mix. The grower left us with a
month’s worth of marijuana tea, glycerine, and olive
oil — and a cookie recipe. We paid $80.
“We made the cookies with the marijuana olive oil,
starting J off with half a small cookie. J normally goes
to bed around 7:30 p.m.; by 6:30 he declared he was
tired and conked out. As we anxiously peeked in on
him, half-expecting some red-eyed ogre from Reefer
Madness to come leaping out at us, we saw instead
that he was sleeping peacefully. Usually, his sleep is
preparing for a trip to the park, J disappeared, and we
wondered if he was going to throw one of his tantrums.
Instead, he returned with Grandma’s shoes, laying them
in front of her, even carefully adjusting them so that
they were parallel. He looked into her face, and smiled.
“It’s strange, I’ve come to think, that the virtues
of such a useful and harmless botanical have been so
clouded by stigma. Meanwhile, in treating J with pot,
we are following the law — and the Hippocratic oath:
first, do no harm. The drugs that our insurance would
pay for — and that the people around us would support
without question — pose real risks to children. For
now, we’re sticking with the weed.
“How is J doing now, four months into our cannabis
experiment? Well, one day recently, he came home
from school, and I noticed something really different:
He had a whole shirt on.
“Pre-pot, J ate things that weren’t food. He chewed
the collar of his T-shirts while stealthily deconstructing
them from the bottom up, teasing apart and then
swallowing the threads. His chewing become so uncontrollable
we couldn’t let him sleep with a pajama
top (it would be gone by morning) or a pillow (ditto
the case and the stuffing). The worst part was watching
him scream in pain on the toilet, when what went in
had to come out.
“Almost immediately after we started the cannabis,
this stopped. Just stopped. J now sleeps with his organic
wool-and-cotton, temptingly chewable comforter. He
pulls it up to his chin at night and declares, ‘I’m cozy!’
“Next, we started seeing changes in J’s school
reports. At one August parent meeting, his teacher
excitedly presented his June-July ‘aggression’ chart.
For the past year, he’d consistently had 30 to 50 aggressions
in a school day, with a one-time high of 300.
The charts for June through July, by contrast, showed
he was actually having days —sometimes one after
another—with zero aggressions.
“I don’t consider marijuana a miracle cure for autism.
But I do consider it a wonderful, safe botanical
that allows J to participate more fully in life without
the dangers and sometimes permanent side effects of
pharmaceutical drugs, now that we have a good dose
and a good strain. Free from pain, J can go to school
and learn. And his violent behavior won’t put him in
the local children’s psychiatric hospital —a scenario
all too common among his peers.
“We have pictures of J from a year ago when he
would actually claw at his own face. That little child
with the horrifically bleeding and scabbed face looks
to us now like a visitor from another world. The J we
know now just looks like a happy little boy.
“We worried that ‘the munchies’ would severely
aggravate J’s problems with overeating in response
to his stomach pangs. Instead, the marijuana seems to
have modulated these symptoms. J still can get overexcited
if he likes a food too much, so the other day,
we dared to experiment with doenjang, a tofu soup
continued on next page
Parents of some autistic children report that cannabis eases behavioral
problems more effectively than conventional pharmaceuticals. Their
anecdotal evidence should be taken seriously by medical researchers.
photo by George Heyer
shallow and restless.
“When J decided he didn’t like the cookie anymore,
we switched to the tea. After two weeks,
we noticed a slight but consistent lessening of
aggression. Since we started him on his ‘special
tea,’ J’s face, which is sometimes a mask of pain,
has softened. He smiles more. For the last year,
his individual education plan at his special-needs
school was full of blanks because he spent his
whole day in an irritated, frustrated mess. Now,
April’s report shows real progress, including
“two community outings with the absence of
aggressions.”
“The big test has been a visit from Grandma.
The last time she came, J hit her. This time,
she remarked that J seems calmer. As we were
Since we started him on his ‘special
tea,’ J’s face, which is sometimes a mask
of pain, has softened.
Lester Grinspoon, MD, Associate Professor Emeritus of
Psychiatry at Harvard Medical School, was the first U.S.
doctor to prescribe lithium carbonate for bipolar disorder.
While writing Marihuana Reconsidered (Harvard, 1971) he
became convinced that the plant was beneficial. Marihuana:
The Forbidden Medicine (with James Bakalar, Yale, 1997)
lists its wide range of applications.
O’Shaughnessy’s • Summer 2010
that he used to love as a baby. The last
time we tried it, a year ago, he frisbeed
the bowl against a tile wall.
“We left J in the kitchen with his
steamy bowl and went to the adjoining
room. We heard the spoon ding. Satisfied
slurpy noises. Then a strange noise that
we couldn’t identify. A chkkka bsssshhht
doinnng! We returned to the kitchen, half
expecting to see the walls painted with
doenjang. Everything was clean. The
bowl and spoon, however, were gone.
“J had taken his dishes to the sink,
rinsed them, and put them in the dishwasher
—something we’d never shown
him how to do. In four months, he’d
gone from a boy we couldn’t feed to a
boy who could feed himself and clean
up after. The sight of the bowl, not quite
rinsed, but almost, was one of the sweetest
sights of my parental life. I expect
more to come.”
Because autism is such a devastating
and so far incurable disease, and
the available pharmaceutical products
have such limited usefulness and serious
side-effects, anguished parents like
Marie Myung-Ok Lee seek out alternative
therapies.
chotic drug risperidone and cannabis,
the latter is the much safer drug.
It is often objected, especially by
federal authorities, that the medical
usefulness of marijuana has not been
demonstrated by controlled studies,
the rigorous, expensive, and time-consuming
tests necessary to win approval
by the Food and Drug Administration
(FDA) for marketing as medicines. The
purpose of the testing is to protect the
consumer by establishing both safety and
efficacy. Because no drug is completely
safe (nontoxic) or always efficacious, a
drug approved by the FDA has presumably
satisfied a risk-benefit analysis.
The cost of doing the controlled studies
necessary for FDA approval may run
to about $800 million per drug, a cost
borne by the drug company seeking it as
a necessary pre-requisite for the distribution
of its patented product. Because it
is impossible to patent a plant, pharmaceutical
companies are not interested in
developing this herbal medicine and so
far the cannabinoid products they have
developed are not nearly as useful as
whole herbal marijuana.
Should FDA Rules Apply?
But it is doubtful whether FDA rules
should apply to marijuana. First, there is
no question about its safety. It has been
used for thousands of years by millions
of people with very little evidence of
significant toxicity. Similarly, given the
mountain of anecdotal evidence which
has accumulated over the years, no
double-blind studies are needed to prove
marijuana’s efficacy. Any astute clinician
who has experience with patients
who have used cannabis as a medicine
knows that it is efficacious for many
people with various symptoms and
syndromes. What we do not know is
what proportion of patients with a given
symptom will get relief from cannabis
and how many will be better off with
cannabis than with the best presently
available medicine. Here large, controlled
studies will be helpful.
Controlled experiments were
not needed to recognize the
therapeutic potential of chloral
hydrate, barbiturates, aspirin,
curare, insulin, or penicillin.
Physicians also have available evidence
of a different kind, whose value
is often underestimated. Anecdotal
evidence commands much less attention
than it once did, yet it is the source
of much of our knowledge of synthetic
medicines as well as plant derivatives.
Controlled experiments were not needed
to recognize the therapeutic potential of
chloral hydrate, barbiturates, aspirin,
curare, insulin, or penicillin. Furthermore,
it was through anecdotal evidence
that we learned of the usefulness of
propranolol for angina and hypertension,
of diazepam for status epilepticus
(a state of continuous seizure activity),
and of imipramine for childhood enuresis
(bed-wetting) although these drugs
were originally approved by the FDA
for other purposes. Anecdotes or case
histories of the kind presented here by
Marie Myung-Ok Lee are, in a sense,
the smallest research
studies of all.
Anecdotes present
a problem that
has always haunted
medicine: the anecdotal
fallacy or the
fallacy of the enumeration
of favorable
circumstances
(counting the hits
and ignoring the
misses). If many
Cannabis for Autism from page 3
The first obstacle in the path
of anyone who wishes to explore
cannabis as a medicine
is to overcome the widely held
belief that it is a very dangerous
substance.
There are now available marijuana
cookbooks from which a variety of
edibles which appeal to children can
be found. (See article at right) With
ingestion, the therapeutic effects will
not appear before one and a half to two
hours, but the advantage is that they
last for many hours.
Beyond preparing the edible are
the challenges of determining the right
dose (such as beginning with a fraction
of a cookie and increasing the dose as
needed) and establishing a schedule for
taking the medication. These tasks will
require some experimentation on the
part of the parents, but with experience
they will soon find the best recipes for
their child, the ideal dose and a workable
schedule. Unfortunately, because
there is presently no easy and available
way of knowing with any precision
the potency of any particular batch
of marijuana, each newly prepared
edible will have to be re-titrated, but
with experience caregivers will find
this an increasingly less difficult task.
It is also important to remember that
cannabis is a very forgiving medicine;
one would have to be considerably
over the “ideal” dosage mark to cause
any difficulty.
One way of minimizing what are
usually minor therapeutic differences
between one batch of cannabis and
another is to try to use the same strain
of marijuana every time an edible is
prepared. At the same time, many patients
who use marijuana as a medicine
take advantage of the fact that there is
a growing variety of available strains,
each with slight differences in the
percentages and ratios of the different
therapeutic cannabinoids. This allows
patients to empirically explore the different
strains in an effort to identify
the particular strain which appears to
be the therapeutically most useful for
their symptomatology.
The parents of autistic children
carry a heavy burden. They are constantly
challenged and frustrated by
the child’s inability to communicate,
his impulsiveness and his destructive
and self-destructive behavior. They and
other caregivers become emotionally
drained and physically exhausted from
the constant need for supervision. It is
my hope that this paper will bring to
the attention of many of these parents
the possibility that there may be a new,
if not officially or even medically approved,
approach to their daunting
challenge. While this approach may
not work for all, it assuredly will do
no harm.
people suffering from, say, muscle spasms
caused by multiple sclerosis take cannabis
and only a few get much better relief
than they could get from conventional
drugs, these few patients would stand
out and come to our attention. They and
their physicians would understandably
be enthusiastic about cannabis and might
proselytize for it. These people are not
dishonest, but they are not dispassionate
observers. Therefore, some may regard
it as irresponsible to suggest on the basis
of anecdotes that cannabis may help
some people with a variety of symptoms
and disorders. That might be a problem
if marijuana were a dangerous drug, but
it is becoming increasingly clear that it
is remarkably safe. Even in the unlikely
event that only a few autistic children get
the kind of relief that “J” gets, it could be
argued that cannabis should be available
for them because it costs so little to produce,
the risks are so small, and the results
so impressive.
While federal law is absolute in prohibiting
the use of marijuana for any purpose,
beginning with California in 1996, there
are now 14 states where it is possible
to use it as a medicine within specified
limits. California, in addition to being the
first state to make an accommodation to
patients in need of cannabis, is also one
of the states in which the legal interpretation
of those needs and the means by
which they can be filled is broad enough
to satisfy the demands of patients with the
wide variety of symptoms and syndromes
for which this herb is useful.
New Jersey, the latest state to adopt
medical marijuana legislation, is, unfortunately,
among the most restrictive. It is so
restrictive both with respect to the symptoms
and syndromes for which a patient
is allowed to use the drug and the means
by which patients are allowed access to
it, that only a relatively small percentage
of the patients who would find marijuana
more useful, less toxic, and less expensive
than the conventional drugs they presently
use will have access to it. Fortunately for
her and her family, Marie Myung-Ok Lee
lives in Rhode Island, where after presenting
the appropriate credentials from
J’s physician, she was licensed to legally
obtain marijuana. However, in most states
patients or the people responsible for their
care have to make, what for many of them,
is a very difficult decision —whether to
buy or grow cannabis outside of the law.
Beyond gaining access to marijuana,
there are the problems involved in the
preparation of this medicine in a form suitable
for children. The most common way
in which marijuana is used as a medicine
is through inhalation of the smoke from
a pipe, a joint or a vaporizer. This is the
preferred method for adults, because it
makes it possible for the patients to precisely
titrate the dose because with this
method of delivery they will perceive
the therapeutic effects within minutes.
However, inhalation is not an option for
children who suffer from autism; for these
patients, the best route for administration
is oral, in the form of cookies, brownies,
tea, etc.
I have had the opportunity to consult
with and help a small number of these
parents explore marijuana as a medicine
which can help to control some of
the severe behavioral problems. (For
the approximately one in five children
with autism who suffer some sort of
seizure disorder, it is important to note
that marijuana is an excellent anticonvulsant
and was widely used as such in
the last part of the 19th century and the
early decades of the 20th). Those who
have persevered in the arduous process
of both finding the correct oral vehicle
and titrating the optimal dose have been
rewarded in more or less the same ways
as J’s parents.
The first obstacle in the path of anyone
who wishes to explore cannabis as a
medicine is to overcome the widely held
belief that it is a very dangerous substance.
The misinformation campaigns
of the United States government and
such organizations as the Partnership for
a Drug-Free America notwithstanding,
marijuana is an unusually safe drug. In
fact, after federal-court-ordered lengthy
hearings before a Drug Enforcement
Administration Law Judge involving
many witnesses, including both patients
and doctors, and thousands of pages
of documentation, Judge Francis L.
Young in 1988 asserted that “marijuana,
in its natural form, is one of the safest
therapeutic active substances known to
man…”
Cannabis was much used in Western
medicine from the mid-19th century
until shortly after the passage of the
Marijuana Tax Act of 1937. There has
never been a recorded death attributable
to marijuana. When it regains its rightful
place in the US pharmacopeia, it will
soon be recognized as one of the least
toxic medicines in that compendium.
While there are no studies of the toxicity
of cannabis in children, neither are there
pediatric studies of the toxicity of risperidone
and other conventional drugs used
in the treatment of autism. However, to
the extent that one can extrapolate the
adult toxicity profiles of the antipsyCopyright
2013 by O’Shaughnessy’s. All rights reserved.
 

Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders.

Author information

1
Division of Pharmacology, Department of Experimental Medicine, Second University of Naples, via S. Maria di Costantinopoli, 16, 80138, Naples, Italy, dariosin@uab.edu.

Abstract

Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3-9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care.

Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders.

William Paterson University, Wayne, USA.

Abstract

Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Δ(9)-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

Targeting the endocannabinoid system in the treatment of fragile X syndrome.

Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Abstract

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation. The Fmr1 knockout model recapitulates the main traits of the disease. Uncontrolled activity of metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) signaling seem crucial in the pathology of this disease. The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice. We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.

 

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