This is a follow up to a previous post, Understanding CDC Prevalence Estimates.

It is a popular misconception that there is a growing autism epidemic in the US based in part on the changing prevalence numbers reported by the CDC. But given that the CDC is monitoring a sample of those most likely to develop autism one cannot make the claim that there is an epidemic. To the contrary, it is still unclear how many autistic people there are. The most accurate conclusion that can be drawn about the size of the population of autistic individuals using the changing CDC prevalence data is that more of the children most likely to have a developmental disorder at the ADDM sites are being diagnosed and receiving treatment.

So what can the CDC prevalence numbers tell us if they can’t be generalized to the whole population? Plenty. First, we see that race and ethnicity influences identifying ASD and also IQ placement. Second, while it is established in the scientific literature that ASD can be diagnosed as early as 12 months of age it is more commonly identified at 53 months. This suggests that something is causing a delay in diagnosis. Third, boys are still more often diagnosed than girls. Fourth, despite developmental concerns being noted for a number of the children seen at the monitoring sites these concerns did not always generate a comprehensive evaluation for the child in question.

What can parents take away from this discussion of CDC prevalence numbers? Take a second critical look at those making claims about there being an epidemic of autism because, frankly, the numbers available to us do not support such claims. If you as a parent have concerns about your child’s developmental progress push for a comprehensive evaluation of your child. Don’t be put off or take a wait and see approach.

In the United States the Centers for Disease Control and Prevention (CDC) maintains a network of 11 autism monitoring sites across the country known as the Autism and Developmental Disabilities Monitoring (ADDM) Network. Published numbers on prevalence from the CDC come from observations at these sites. The CDC typically publishes the latest prevalence numbers available in the Morbidity and Mortality Weekly Report (MMWR) Surveillance Summaries. This publication is available for viewing and download on the CDC website www.cdc.gov. The prevalence estimate published in March 2014 (1 in 68, or 14.7 per 1,000) was based on ADDM network observations from 2010.

First let’s define some terms. You may hear in the terms prevalence and incidence used interchangeably in the numbers discussion surrounding autism. However, prevalence and incidence are not the same. There are two types of prevalence to be aware of in this discussion. Point prevalence is a ratio representing the portion of a population that has a condition at a single point in time, point x. Period prevalence is a measure of the portion of a population that has a condition in a set span of time, period x to y. Incidence is the rate at which new cases of a condition occur per person over a period time. Cumulative incidence is the proportion of a population that became new cases within a specified time period. Research is generally focused on point and period prevalence of autism spectrum disorders.


The CDC has been monitoring ASD through the ADDM network since 2000 The following are the criteria, as reported in the MMWR Surveillance Summaries (pp. 3, 4), for inclusion in the cohort samples monitored by the CDC at the ADDM sites.

1.       Birth year (children 8 years old during surveillance period) and residency. (children must live in the areas covered by the ADDM sites during the period of surveillance). This is the age by which diagnosis of a developmental disorder is most likely to have been made.

2.       Eligible for special education services, have an International Classification of Diseases, Ninth Revision (ICD 9) disability or psychological condition.

3.       The presence of certain behavioral or diagnostic descriptions in the children’s files.

4.       A diagnosis of disability upon review by trained clinicians blinded to any identifying information about the children based on DSM-IV-TR criteria.

The first criteria, birth year and residency, define the population from which the CDC draws its samples. From this population a sample is taken, based on the remaining criteria, to determine the prevalence of autism spectrum disorders. This selection process presents one of the first problems with the CDC prevalence data. The sample of children monitored by the CDC is not representative of the population of children in the US. The children monitored at the ADDM sites are chosen because they have a greater likelihood of having a developmental disorder. Furthermore, the ADDM sites themselves are not randomly distributed and do not provide a true representation of the US population. This biased sample means that the prevalence numbers reported by the CDC cannot be used to make inferences about the population as a whole. While the CDC makes it clear that these are limitations to their surveillance data these points seem to go ignored by the public.


See the follow up post, CDC Prevalence Estimates and ASD Epidemic.

This post is part of the series Examining the Use of Medical Marijuana for ASD Treatment.

As written the current New York State medical marijuana law does not include ASD in the list of conditions that may be treated with medical marijuana. The following are the only conditions for which medical marijuana use is approved in New York State:

·         Cancer

·         positive status for HIV or AIDS

·         ALS

·         Parkinson’s disease

·         multiple sclerosis

·         damage to the nervous tissues of the spinal cord with objective neurological indication of intractable spasticity

·         epilepsy

·         inflammatory bowel disease

·         neuropathies

·         Huntington’s disease

Included in the New York state legislation is a provision that this list may be amended at will. The legislation also spells out other conditions not necessarily specific to a disease that may be treated with medical marijuana. These include:

·         cachexia or wasting syndrome

·         severe chronic pain

·         severe nausea

·         seizures

·         severe or persistent muscle spasm

Again there is the provision that this list may be amended at will. Furthermore, there is a provision to consider adding the following conditions to the approved medical marijuana conditions list after 18 months:

·         Alzheimer’s

·         muscular dystrophy

·         dystonia

·         post-traumatic stress disorder

·         rheumatoid arthritis

The law does not provide any guidelines as to how to evaluate a given condition for potential inclusion in the approved medical marijuana conditions list.

Patients and providers will be required to be certified and to register in order to prescribe, dispense, and use only those medical marijuana products approved by the state. Certified patients will be required to carry registration cards identifying themselves as certified users of medical marijuana or they will risk prosecution pursuant to existing laws regarding illegal drugs. There is enumerated in the bill regulations for those designated as caregivers of certified patients.

There are also provisions in the law requiring manufacturers and providers to register to manufacture and to provide medical marijuana products. The law also requires these companies to submit their products to laboratory testing in labs approved by the state. It is not clear what standards regarding reporting of levels of active ingredients, content labeling, and reporting of adverse effects manufacturers will be subject to.

While the current legislation does not require insurers to cover medical marijuana the cost of various medical marijuana preparations will be set by the state rather than the manufacturers producing the medical marijuana products. The majority of the language of the bill deals with managing the potential revenue generated by the manufacture and sale of medical marijuana products in New York state.


For more information see ASD and Medical Marijuana References.

This post is part of the series Examining the Use of Medical Marijuana for ASD Treatment.

Given the apparent disregulation of activity in and between various neuronal networks in the autistic brain it is easy to see the appeal of marijuana to artificially stimulate the endocannabinoid system. But it is unclear what happens when you try to artificially stimulate the brain’s natural breaking system. One must proceed with the same caution one would employ when evaluating the use of other pharmaceuticals commonly prescribed to treat some of the symptoms and behaviors common in ASD.

It is important for parents to be aware of marijuana intoxication syndrome. In typically functioning individuals symptoms can range from giddiness to depression, introspection, and a sense of time moving slowly. How an autistic individual may react will depend on the baseline function of their endocannabinoid system.

Endocannabinoid system functionality is complex. We don’t have a reliable way to measure it. In fact we are still learning how this system works. Since we as yet have no way to measure endocannabinoid functionality parents will have to keep meticulous notes on their child’s behavior before, during, and after administering the preferred Cannabis product. A few of the many areas to monitor are:

·         motor function (walking, running, hand-eye coordination)

·         stability of mood

·         appetite

·         responses to stressful or new environments

·         blood pressure

·         sleep-wake cycle

Keep in mind that you may see improvement or deterioration in these and other areas with the administration of cannabinoids. Also keep in mind that your evaluation of functionality in these areas will be somewhat subjective. Consider having one or more independent observers, who are unaware of when or if your child has been administered a preparation of cannabinoids, monitor these areas as well.

Further consideration should be given to the following factors before making a decision about using medical ma. There has been little scientific research into the use of Cannabis products for the treatment of ASD. It also remains unclear what, if any, side effects may manifest in children with ASD given Cannabis products for any length of time. While the manufacturers of drugs for medical use are regulated and required by law to provide information about composition and efficacy of their products the manufacturers of Cannabis products are not. Furthermore, while drug companies are required to track and disclose any possible side effects of the products no such requirements currently exist for the manufacturers of Cannabis products. It remains unclear if manufacturers of Cannabis products will be subject to regulation similar to that of other drug companies. Currently New York State does not have a legal manufacturing base for Cannabis products. It remains to be seen whether or not one will be established.


Next up, NYS Medical Marijuana Law Summary.

This post is part of the series Examining the Use of Medical Marijuana for ASD Treatment.

References

Adams, M. (2013, October 31). Marijuana May Be Used to Treat Autism. Retrieved from www.hightimes.com: http://www.hightimes.com/read/marijuana-may-be-used-treat-autism

Anthony, H. (2014, May 7). Medical Cannabis Treats Autism. Retrieved from guardianlv.com: http://guardianlv.com/2014/05/medical-cannabis-treats-autism/

Buglione, N. (n.d.). Marijuana Madness. Retrieved from www.autismsupportnetwork.com: http://www.autismsupportnetwork.com/news/autism-treatment-marijuana-madness-8763721

Busquets-Garcia, A., Maldonado, R., & Ozaita, A. (2014, August). New insights into the molecular pathophysiology of fragile X syndrome and therapeutic perspectives from the animal model. The International Journal of Biochemistry & Cell Biology, 53, 121-126. doi:10.1016/j.biocel.2014.05.004

Governor Cuomo Signs Bill to Establish Comprehensive Medical Marijuana Program. (2014, July 7). Retrieved from www.governor.ny.gov: http://www.governor.ny.gov/press/07072014-comprehensive-medical-marijuana-program

Jew, C. P., Wu, C.-S., Sun, H., Zhu, J., Huang, J.-Y., Yu, D., . . . Lu, H.-C. (2013, August). mGluR5 Ablation in Cortical Glutamatergic Neurons Increases Novelty-Induced Locomotion. PLoS ONE, 8(8), 1-18. doi:10.1371/journal.pone.0070415

Kerr, D., Downey, L., Conboy, M., Finn, D., & Roche, M. (2013, July). Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behavioural Brain Research, 249, 124-132. doi:10.1016/j.bbr.2013.04.043

Miles, K. (2012, Septmeber 27). Marijuana-Like Chemical May Help Autism And Fragile X Syndrome Symptoms. Retrieved from www.huffingtonpost.com: http://www.huffingtonpost.com/2012/09/27/marijuana-chemical-autism-fragile-x_n_1920320.html

Mom: Marijuana Saved My Autistic Son's Life (VIDEO). (2010, March 18). Retrieved from www.huffingtonpost.com: http://www.huffingtonpost.com/2009/11/23/mom-marijuana-saved-my-au_n_368246.html

Mosbergen, D. (2013, January 31). Alex Echols, Boy With Autism, Gets Medical Marijuana To Manage Self-Destructive Rages (VIDEO). Retrieved from www.huffingtonpost.com: Alex Echols, Boy With Autism, Gets Medical Marijuana To Manage Self-Destructive Rages

Nestler, E. J., Hyman, S. E., & Malenka, R. C. (2009). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill.

Program Bill # 57 Medical Marihuana. (2014, June 19). Retrieved from www.governor.ny.gov: http://www.governor.ny.gov/sites/default/files/documents/GPB-57-MEDICAL-MARIHUANA_BILL.pdf

Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., LaMantia, A.-S., & White, L. (Eds.). (2012). Neuroscience (5th ed.). Sunderland, MA: Sinauer.

Siniscalco, D., Sapone, A., Giordano, C., Cirillo, A., Magistris, L., Rossi, F., . . . Antonucci, N. (2013, November). Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders. Journal of Autism & Developmental Disorders, 43(11), 2686-2695. doi:10.1007/s10803-013-1824-9

Terzian, A. L., Micale, V., & Wotjak, C. T. (2014, July). Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex-dependent social interest in mice. European Journal of Neuroscience, 40(1), 2293-2298. doi:10.1111/ejn.12561

von dem Hagen, E. A., Stoyanova, R. S., Baron-Cohen, S., & Calder, A. J. (2013, August). Reduced functional connectivity within and between 'social' resting state networks in autism spectrum conditions. Social Cognitive and Affective Neuroscience, 8(6), 694–701. doi:10.1093/scan/nss053

Yandell, K. (2013, April 11). A Link Between Autism and Cannabinoids: Mutations tied to autism in mice lead to deficits in the signaling pathway activated by marijuana. Retrieved from www.the-scientist.com: http://www.the-scientist.com/?articles.view/articleNo/35088/title/A-Link-Between-Autism-and-Cannabinoids/

This post is part of the series Examining the Use of Medical Marijuana for ASD Treatment.

Research into the relationship between ASD and the functionality of the endocannabinoid system is still in its infancy. However, given current knowledge of how the human brain typically develops and functions along with what we currently know about ASD we can speculate about how the endocannabinoid system may function in individuals with ASD. There are several possibilities to consider in three categories, the endocannabinoids themselves, the degradative enzymes that terminate endocannabinoid activity, and the function of endocannabinoid receptors.

1.      Endocannabinoids

a.       Not enough endocannabinoids produced leading to insufficient inhibition of certain neuronal signals and networks.

b.      Too many endocannabinoids produced leading to too much inhibition of certain neuronal signals and networks.

2.      Degradative Enzymes

a.       Increased enzyme function leading to a decrease in endocannabinoid activity.

b.      Under or inactive enzymes leading to an increase in endocannabinoid activity.

3.      Receptors

a.       Too many receptors.

b.      Not enough receptors.

c.       Malformed receptors.

Any of these factors, in any combination, in any number of the brain regions regulated by the endocannabinoid system may give rise to the various symptoms and behaviors we have come to associate with ASD.


Next up, ASD and the Cannabinoids.

This post is part of the series Examining the Use of Medical Marijuana for ASD Treatment.

The cannabinoids are the active compounds in marijuana. They take their name from the scientific names of the plants used to make marijuana, usually Cannabis sativa and Cannabis indica. There are many cannabinoid compounds that are found in plants of the genus Cannabis but delta-9-tetrahydrocannabinol (THC) is the one that receives the most attention because of its known psychoactive effects. The following have been reported among the short term effects of THC: euphoria, disinhibition, cognitive deficits, increased hunger, and alteration of sensory perception. Withdrawal of THC after short term use leads to: irritability, restlessness, sleep disturbance, and nausea. Long term use leads to the accumulation of THC in the tissues of the body. Since the brain has no mechanism for breaking down THC, or any of the other cannabinoids, they tend to persist in the brain.

Like many other psychoactive drugs THC induces the release of dopamine, the neurotransmitter that plays a major role in the reward, motivation, and decision making processes in the brain. Continued exposure to the cannabinoids leads to a lasting decrease in the strength of the connections between neurons having a depressive effect on their functioning.

There is a limited amount of formal research available on the effects of other cannabinoids as well as the potential therapeutic uses of THC.


Next up, ASD and the Endocannabinoid System.