While there is preliminary evidence that CBD may have therapeutic value for a number of conditions, we need to be careful to not get ahead of the evidence.

Ninety-five percent of drugs that move from promising preclinical findings to clinical research do not make it to market. The recently announced elimination of the PHS review of non-federally funded research protocols involving marijuana is an important first step to enhance conducting research on marijuana and its components such as CBD. Still, it is important to try to understand the reasons for the lack of well-controlled clinical trials of CBD including: the regulatory requirements associated with doing research with Schedule I substances, including a requirement to demonstrate institutional review board approval; and the lack of CBD that has been produced under the guidance of Current Good Manufacturing Processes (cGMP) – required for testing in human clinical trials – available for researchers. Furthermore, the opportunity to gather important information on clinical outcomes through practical (non-randomized) trials for patients using CBD products available in state marijuana dispensaries is complicated by the variable quality and purity of CBD from these sources. Ongoing CBD Research The NIH recognizes the need for additional research on the therapeutic effects of CBD and other cannabinoids, and supports ongoing efforts to reduce barriers to research in this area. 

NIH is currently supporting a number of Element X studies on the therapeutic effects as well as the health risks of cannabinoids. These include studies of the therapeutic value of CBD for: Treatment of substance use disorders (opioids, alcohol, cannabis, methamphetamine) Attenuation of the cognitive deficits caused by THC Neuropathic pain due to spinal cord injury Mitigating the impact of cannabis use on risk for schizophrenia Examination of the potential of CBD as an antiepileptic treatment It is important to note that NIDA’s mission is focused on drug abuse; studies related to the therapeutic effects of CBD in other areas would be funded by the Institute or Center responsible for that program area. For example, studies related to epilepsy will likely be funded by the National Institute of Neurological Disorders and Stroke or by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, while studies related to schizophrenia will likely be funded by the National Institute on Mental Health. Conclusion There is significant preliminary research supporting the potential therapeutic value of CBD, and while it is not yet sufficient to support drug approval, it highlights the need for rigorous clinical research in this area. There are barriers that should be addressed to facilitate more research in this area. 

We appreciate the opportunity to testify on the potential use of CBD for therapeutic purposes. Thank you again for inviting me here today, and I look forward to any questions you may have. CBD: Everything You Need To Know About Cannabidiol Cannabidiol (CBD) came out to the world in a big way after this simple plant chemical stopped an epileptic seizure in its tracks on U.S. national television. In the time since, many enthusiasts have realized that this miracle compound can stop spasms, calm anxiety, and soothe those in chronic pain. But, what is CBD and how does it work? How is it different from THC? To help you become more familiar with the cannabinoid here is everything you need to know about CBD. What is cannabidiol (CBD)? Cannabidiol (CBD) is one of the most prevalent chemical compounds in the cannabis plant. Unlike the more famous molecule, tetrahydrocannabinol (THC), CBD is completely nonpsychoactive. Don’t expect to get “high” off of this organic chemical, however. CBD is all relaxation without intoxication. While CBD still has an effect on your body, consuming CBD by itself isn’t going to send you on the cerebral adventure associated with THC. For decades, medical professionals and the general public overlooked CBD because psychoactive cannabis took center stage. Now, the medical potential of CBD has taken cannabis to mainstream audiences. Preclinical trials over the past four decades have found that the cannabinoid shows promise as an: anti-inflammatory antioxidant neuroprotectant anxiolytic antidepressant analgesic anti-tumoral agent anti-psychotic CBD is often used by patients in the form of an oil. 

Patients with more chronic conditions such as cancer and epilepsy often use medical cannabis oil extracted from high-CBD varieties of cannabis. How does CBD work? Most predominant inside the resin glands (trichomes) of the female cannabis plant, CBD is one of over 80 chemical compounds known as cannabinoids. Cannabinoids are agonists that bind to special receptors on your cells, called cannabinoid receptors. Certain receptors are heavily concentrated in the central nervous system while others are found in almost every organ of the body. Cannabinoid receptors are even found in the skin, digestive tract, and even in the reproductive organs. You can think of agonists as keys and cannabinoid receptors as locks. By consuming cannabis, you are taking in agonists that interact with different locks on cells in the body. Together, these cell receptors make up a larger endocannabinoid system (ECS). The ECS is a vast network of cell receptor proteins with many functions. Some describe the ECS as the greatest neurotransmitter system in the body. It lends a hand in seemingly just about everything, including: mood memory motor control immune function reproduction pain perception appetite sleep bone development Four primary purposes of the ECS include neuroprotection, stress recovery, immune balance, and homeostatic regulation. 

The last one is a fancy way of referring to a system that creates optimum energy balance in the body. Somehow, CBD seems to tap into this balancing system to produce its therapeutic effects. CBD is able to interact with cells in our bodies because the molecule has a similar composition to similar chemicals that the human body produces naturally, called endocannabinoids. Endo means inside and cannabinoid refers to action on cannabinoid receptors. In contrast, the cannabinoids in the cannabis plant are technically called phytocannabinoids. It’s not often that a plant compound can make headlines over and over again. However, CBD is a phytocannabinoid with some serious life-saving potential. In fact, CBD has only gained mainstream attention quite recently, after the family of one brave little girl decided to throw caution to the wind and speak out about medical cannabis. The beginning of the CBD movement Before she was five years old, Charlotte Figi stopped laughing. While the average child laughs around 300 times a day, Charlotte temporarily lost her ability to communicate due to a rare and severe form of epilepsy called Dravet syndrome. Dravet syndrome affects roughly 1 in 30,000 infants around the globe. Though most Dravet patients begin their lives as healthy children, development quickly begins to regress after the first few months. Intense seizures overtake children as young as three months old. 

These seizures cause them to lose consciousness and convulse for up to a few hours at a time. After years of rushed trips to the emergency room, the Figi’s were desperate. Between unexpected complications, experimental medications, being told that they’ve reached “the end of the line”, they had experienced it all. When there were seemingly out of options, the family finally made a life changing decision. What they didn’t know was that their choice would ultimately spur a social movement and, more importantly, bring their daughter back to life. The Figi’s decided to treat their daughter with cannabidiol (CBD), one of the primary compounds found in the marijuana plant. CBD: Underappreciated for too long When Paige and Matt Figi first began their search for nonpsychoactive cannabis in Colorado, they fell upon some tough luck. Since the 1980s, marijuana breeders have had one major goal: creating the most potent, psychoactive cannabis out there. The competition is tough. After nearly three decades of rising demands for psychoactive cannabis, it’s not uncommon to walk into a dispensary today and find cannabis with THC content over 20%. By comparison, cannabis in the 70s contained an average of 6 to 8%. Focusing on THC content alone meant growers overlooked CBD during the hybridization process, making access nearly impossible for anyone hoping to experiment with CBD as medicine. 

Fortunately for children like Charlotte, one Colorado family was ahead of the curve. The Stanley Brothers had been developing exactly the plant the Figi’s had been searching for: a strain high in CBD and low in THC. High-CBD/ low-THC strains have little, if any, psychoactive effect. Rather, anecdotal reports and preclinical studies suggest that high-CBD cannabis can calm excitability without causing cognitive impairment. Before making the final decision to try CBD as a treatment, Charlotte was having 300 grand mal seizures a week, one every 15 minutes. After adding CBD oil to her daily routine? CBD kept Charlotte’s seizures at bay for an entire week. The Figi’s were astonished. I didn’t hear her laugh for six months. I didn’t hear her voice at all, just her crying. I can’t imagine that I would be watching her making these gains that she’s making, doing the things that she’s doing (without the medical marijuana). I don’t take it for granted. Every day is a blessing. – Paige Figi CNN first aired Charlotte’s story in 2013. Since then, CBD has been making headlines all over the world.

The trigeminal nerve is a mixed nerve that carries the general somatic senses from the head, similar to those coming through spinal nerves from the rest of the body.

Testing smell is straightforward, as common smells are presented to one nostril at a time. The patient should be able to recognize the smell of coffee or mint, indicating the proper functioning of the olfactory system. Loss of the sense of smell is called anosmia and can be lost following blunt trauma to the head or through aging. The short axons of the first cranial nerve regenerate on a regular basis. The neurons in the olfactory epithelium have a limited life span, and new cells grow to replace the ones that die off. The axons from these neurons grow back into the CNS by following the existing axons—representing one of the few examples of such growth in the mature nervous system. If all of the fibers are sheared when the brain moves within the cranium, such as in a motor vehicle accident, then no axons can find their way back to the olfactory bulb to re-establish connections. If the nerve is not completely severed, the anosmia may be temporary as new neurons can eventually reconnect. Olfaction is not the pre-eminent sense, but its loss can be quite detrimental. The enjoyment of food is largely based on our sense of smell. Anosmia means that food will not seem to have the same taste, though the gustatory sense is intact, and food will often be described as being bland. However, the taste of food can be improved by adding ingredients (e.g., salt) that stimulate the gustatory sense. Testing vision relies on the tests that are common in an optometry office. 

The Snellen chart ([link]) demonstrates visual acuity by Focused In presenting standard Roman letters in a variety of sizes. The result of this test is a rough generalization of the acuity of a person based on the normal accepted acuity, such that a letter that subtends a visual angle of 5 minutes of an arc at 20 feet can be seen. To have 20/60 vision, for example, means that the smallest letters that a person can see at a 20-foot distance could be seen by a person with normal acuity from 60 feet away. Testing the extent of the visual field means that the examiner can establish the boundaries of peripheral vision as simply as holding their hands out to either side and asking the patient when the fingers are no longer visible without moving the eyes to track them. If it is necessary, further tests can establish the perceptions in the visual fields. Physical inspection of the optic disk, or where the optic nerve emerges from the eye, can be accomplished by looking through the pupil with an ophthalmoscope. The Snellen chart for visual acuity presents a limited number of Roman letters in lines of decreasing size. The line with letters that subtend 5 minutes of an arc from 20 feet represents the smallest letters that a person with normal acuity should be able to read at that distance. The different sizes of letters in the other lines represent rough approximations of what a person of normal acuity can read at different distances. 

For example, the line that represents 20/200 vision would have larger letters so that they are legible to the person with normal acuity at 200 feet. The optic nerves from both sides enter the cranium through the respective optic canals and meet at the optic chiasm at which fibers sort such that the two halves of the visual field are processed by the opposite sides of the brain. Deficits in visual field perception often suggest damage along the length of the optic pathway between the orbit and the diencephalon. For example, loss of peripheral vision may be the result of a pituitary tumor pressing on the optic chiasm ([link]). The pituitary, seated in the sella turcica of the sphenoid bone, is directly inferior to the optic chiasm. The axons that decussate in the chiasm are from the medial retinae of either eye, and therefore carry information from the peripheral visual field. Pituitary Tumor The left panel of this figure shows the top view of the brain. The center panel shows the magnified view of a normal pituitary, and the right panel shows a pituitary tumor. The pituitary gland is located in the sella turcica of the sphenoid bone within the cranial floor, placing it immediately inferior to the optic chiasm. If the pituitary gland develops a tumor, it can press against the fibers crossing in the chiasm. Those fibers are conveying peripheral visual information to the opposite side of the brain, so the patient will experience “tunnel vision”—meaning that only the central visual field will be perceived. The vestibulocochlear nerve (CN VIII) carries both equilibrium and auditory sensations from the inner ear to the medulla. 

Though the two senses are not directly related, anatomy is mirrored in the two systems. Problems with balance, such as vertigo, and deficits in hearing may both point to problems with the inner ear. Within the petrous region of the temporal bone is the bony labyrinth of the inner ear. The vestibule is the portion for equilibrium, composed of the utricle, saccule, and the three semicircular canals. The cochlea is responsible for transducing sound waves into a neural signal. The sensory nerves from these two structures travel side-by-side as the vestibulocochlear nerve, though they are really separate divisions. They both emerge from the inner ear, pass through the internal auditory meatus, and synapse in nuclei of the superior medulla. Though they are part of distinct sensory systems, the vestibular nuclei and the cochlear nuclei are close neighbors with adjacent inputs. Deficits in one or both systems could occur from damage that encompasses structures close to both. Damage to structures near the two nuclei can result in deficits to one or both systems. Balance or hearing deficits may be the result of damage to the middle or inner ear structures. Ménière's disease is a disorder that can affect both equilibrium and audition in a variety of ways. The patient can suffer from vertigo, a low-frequency ringing in the ears, or a loss of hearing. From patient to patient, the exact presentation of the disease can be different. Additionally, within a single patient, the symptoms and signs may change as the disease progresses. 

Use of the neurological exam subtests for the vestibulocochlear nerve illuminates the changes a patient may go through. The disease appears to be the result of accumulation, or over-production, of fluid in the inner ear, in either the vestibule or cochlea. Tests of equilibrium are important for coordination and gait and are related to other aspects of the neurological exam. The vestibulo-ocular reflex involves the cranial nerves for gaze control. Balance and equilibrium, as tested by the Romberg test, are part of spinal and cerebellar processes and involved in those components of the neurological exam, as discussed later. Hearing is tested by using a tuning fork in a couple of different ways. The Rinne test involves using a tuning fork to distinguish between conductive hearing and sensorineural hearing. Conductive hearing relies on vibrations being conducted through the ossicles of the middle ear. Sensorineural hearing is the transmission of sound stimuli through the neural components of the inner ear and cranial nerve. A vibrating tuning fork is placed on the mastoid process and the patient indicates when the sound produced from this is no longer present. Then the fork is immediately moved to just next to the ear canal so the sound travels through the air. If the sound is not heard through the ear, meaning the sound is conducted better through the temporal bone than through the ossicles, a conductive hearing deficit is present. The Weber test also uses a tuning fork to differentiate between conductive versus sensorineural hearing loss. 

In this test, the tuning fork is placed at the top of the skull, and the sound of the tuning fork reaches both inner ears by travelling through bone. In a healthy patient, the sound would appear equally loud in both ears. With unilateral conductive hearing loss, however, the tuning fork sounds louder in the ear with hearing loss. This is because the sound of the tuning fork has to compete with background noise coming from the outer ear, but in conductive hearing loss, the background noise is blocked in the damaged ear, allowing the tuning fork to sound relatively louder in that ear. With unilateral sensorineural hearing loss, however, damage to the cochlea or associated nervous tissue means that the tuning fork sounds quieter in that ear. The trigeminal system of the head and neck is the equivalent of the ascending spinal cord systems of the dorsal column and the spinothalamic pathways. Somatosensation of the face is conveyed along the nerve to enter the brain stem at the level of the pons. Synapses of those axons, however, are distributed across nuclei found throughout the brain stem. The mesencephalic nucleus processes proprioceptive information of the face, which is the movement and position of facial muscles. It is the sensory component of the jaw-jerk reflex, a stretch reflex of the masseter muscle. The chief nucleus, located in the pons, receives information about light touch as well as proprioceptive information about the mandible, which are both relayed to the thalamus and, ultimately, to the postcentral gyrus of the parietal lobe. 

The spinal trigeminal nucleus, located in the medulla, receives information about crude touch, pain, and temperature to be relayed to the thalamus and cortex. Essentially, the projection through the chief nucleus is analogous to the dorsal column pathway for the body, and the projection through the spinal trigeminal nucleus is analogous to the spinothalamic pathway. Subtests for the sensory component of the trigeminal system are the same as those for the sensory exam targeting the spinal nerves.