CBD Oil Drug Interactions – The CYP Pathway If you are taking a medication affected by cannabidiol, you should consult your doctor to make sure that it is. Describe medical cannabis drug interactions. Describe (prescription THC and CBD are metabolized by CYP3A4 and CYP2C9 (Yamaori et al. Due to an increasing popularity of self-administration of over-the-counter bought CBD, doctors and pharmacists should be aware of its potential.
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She already uses an extract of hemp, a weak form of cannabis bought legally online, with her sons' drug cocktail to control seizures. She hopes medical marijuana would allow her to reduce their reliance on pharmaceuticals that can have significant side effects. Moore also sits on the state's cannabis commission. She said legal concerns about liability are overblown, pointing to a federal appeals court decision that affirms doctors' First Amendment right to discuss marijuana with patients and recommend its use.
President Barack Obama's administration has declined to federally prosecute doctors who comply with state laws permitting medical marijuana.
It's not clear what President-elect Donald J. Trump would do, but he has expressed support for states to be able to decide the issue. I hope more doctors have an open mind about helping patients without a lot of other options.
Patricia Frye, owner of Takoma Park Alternative Care, came out of retirement as a pediatrician a few years ago to recommend medical marijuana via telemedicine to California patients. Now, she sees opportunity in Maryland.
She has studied how marijuana is used for various conditions and said she understands what doses and varieties to recommend that patients use. She would broadly recommend the drug to people who have been diagnosed by their doctors with disease.
She wouldn't recommend it to pregnant women, to minors unless their parents approve, or to people with severe psychiatric conditions unless a mental health doctor is involved with treatment. Karen Clarke-Bennett, a primary care and wellness doctor with the Odenton medical spa A Better You, said she hopes to attract new patients by offering medical marijuana.
She anticipates treating clients with conditions such as seizures, anxiety, arthritis and PTSD. She doesn't plan to market the service until she can learn more about the drug. I am going to take my time and do the appropriate training before I offer anything," Clarke-Bennett said, adding that she has had difficulty finding training opportunities. Some doctors say they may not ever recommend medical marijuana because they fear repercussions from federal authorities, but wanted to put themselves on the Maryland list in case they decide to do so.
One of them is Dr. Nicholas Scotto, a psychiatrist and addiction doctor. While medical marijuana is not approved in Maryland for addiction, he sees a narrow use: Scotto said marijuana could replace or reduce the amount of prescription opioids those patients take and prevent some from going on to abuse drugs. Scotto points to the ongoing opioid addiction epidemic in Maryland and nationwide that has lead to a record number of overdose deaths. Many abusers get their start with a prescription for opioids for pain.
It's a good idea. Right now it's just an idea I was thinking about. Scotto has grappled with addiction and says that's common for practitioners in his field — they become interested in treating addiction because of their own experiences. The state Board of Physicians found Scotto guilty of "unprofessional conduct in the practice of medicine" in the late s. He acknowledged at the time that he was addicted to prescription medications. He complied with the terms of his probation that ended in , according to the Board of Physicians.
Other doctors also said they didn't plan to make medical marijuana a big part of their practices. Devinder Singh, chief and medical director of plastic surgery at Anne Arundel Medical Center , said he would only recommend marijuana for a small number of patients who suffer chronic pain from migraines.
He sees such patients because some can be treated with botox injections or surgery to cut nerves around the scalp. Some of the doctors who signed up don't specialize in areas of medicine for which medical marijuana has an approved use. Several emergency room doctors from the Greater Baltimore Medical Center said they haven't made plans for where and how they would see patients because medical marijuana is for chronic conditions that aren't normally treated in the emergency room.
John Lazarou, a GBMC spokesman, said the hospital has no position on its doctors recommending medical marijuana but emphasized that no one would be recommending the drug in the emergency department. Jeffrey Souryal, one of the GBMC doctors, said he became interested in the medical uses of marijuana after watching his dad die from pancreatic cancer seven years ago. Several doctors who registered with the medical marijuana program listed the addresses of newly created consultancies.
The company has said it opened offices ahead of the program's launch so doctors could establish relationships with patients. Some major health systems said they would not allow their doctors to recommend medical marijuana, including LifeBridge Health , which operates Sinai Hospital in Baltimore as well as other hospitals and medical facilities, and MedStar Health , which has seven hospitals in Maryland and several doctors' offices.
Medical systems may not be able to prevent their doctors from getting into the medical marijuana business on the side, but Ransom said some doctors may not want to go against the wishes of their employers. Other medical providers, including Johns Hopkins and Kaiser Permanente, are still devising policies on medical marijuana.
However, if cognitive dysfunction prevents effective analgesia, opioid rotation may be tried. Psychostimulants including methylphenidate 51 , modafinil 52 , dextroamphetamine 53 , and caffeine 54 have been used. Sympathomimetic side effects of these psychostimulants may be problematic and therapeutic effects of psychostimulants sometimes wanes over time.
Relative contraindications to the use of psychostimulants include preexisting anorexia, severe insomnia, anxiety, paranoid ideation, significant cardiac disease, or poorly controlled hypertension. Nausea is frequently seen at initiation of therapy but persistence of nausea is not commonly seen. Opioids may cause nausea via three mechanisms including a direct effect on the chemoreceptor trigger zone, enhanced vestibular sensitivity, and delayed gastric emptying.
Opioid dosages that have been gradually increased rather than rapidly may prevent nausea. If persistent nausea occurs it is likely in the context of other gastrointestinal systems e. Chronic nausea generally responds to drug therapies for acute nausea 55 including dopamine antagonists [e.
Risperidone was shown in a small observational study to decrease refractory nausea and vomiting due to opioids in advanced cancer patients Opioid rotation may also be considered and has been shown to significantly result in less nausea and vomiting in two studies.
Switching from oral to subcutaneous route produced significantly less nausea and vomiting 59 , Other medications that may help nausea and vomiting include scopolamine patch and meclizine. Acupressure bands and acupuncture may also be helpful. Thought the etiology may be multifactorial from drugs and metabolic derangements, uncontrollable spasms, termed myoclonus is common and dose-related in opioid therapy.
Data was insufficient to affirm benefits of any drug for its management 61 but a low-dose benzodiapine [e. Opioid-induced hyperalgesia is a paradoxical response where patients may become more sensitive to certain painful stimuli. They may experience pain from non-painful stimuli allodynia and the phenomenon is linked to analgesic tolerance.
When suspected, opioid rotation may be an option When therapy is administered according to guidelines, respiratory depression is uncommon but may be seen when rapid increase of opioids is necessary for pain control.
In the setting of sleep apnea or other serious cardiopulmonary comorbidity or when combined with another sedative-hypnotic, the risk of respiratory depression is increased. Careful selection of initial dose and conservative uptitration is necessary. Management with naloxone should be given only in cases of symptomatic respiratory depression or for progressive obtundation. Naloxone can be given in a small bolus injection of dilute solution and repeated doses may be necessary as its half-life is shorter than most opioids.
Naloxone should not be given to somnolent but easily arousable patients. Alternatively, withholding further opioids until respiratory rate improves or pain returns should be considered. Pruritis from morphine is thought to cause histamine release from mast cells although other opioids i. Despite uncertainty, antihistamines are commonly used as first-line agents for opioid-induced pruritis.
Low doses of opioid antagonists are effective treatment for pruritis in patients with non-cancer pain receiving short-term opioids, however interventions in patients receiving long-term use of opioids has not been investigated. Paroxetine according to some anecdotal experience suggests benefit Some evidence exists for use of low doses of opioid antagonists including nalmefene and nalbuphine in the postoperative setting but opioid induced pruritis in long-term use of opioids have not been studied Urinary retention is a result of opioid-induced effects on peripheral nerves that innervate the bladder by increasing the tone of the sphincter and binding to spinal receptors causing total bladder relaxation Initial management consists of catheterization of the bladder and an effort to reduce drugs that could contribute to urinary retention, e.
Other drugs effective in reversing urinary retention include naloxone which also has been shown to reverse analgesia postoperatively Anecdotally, nalbuphine 69 and alpha-1 blockers such as tamsulosin can be used to treat urinary retention in some part related to prostatic hypertrophy.
Adjuvant drugs are sometimes necessary in order to control the many facets of pain. This tenet recognizes that pain is sometimes multifactorial.
Patients may require antidepressants if they remain depressed despite pain control, anxiolytics if the patient remains anxious, as well as corticosteroids, neurolytic, and neurosurgical blocks. The diversity of these drugs has increased dramatically in number in the past few decades.
If and when a patient is unable to achieve adequate analgesia without dose-limiting side effects, a number of things can be considered including optimizing opioid therapy including adjusting the dose or rotating to a different opioid.
The addition of an adjuvant analgesic may also be considered after the opioid dose is optimized. Available adjuvant analgesics include multipurpose analgesics that are used for any type of pain, those used for neuropathic pain, those for bone pain, and those for pain in the setting of bowel obstruction 69 - These medications have broad analgesic efficacy and include glucocorticoids, antidepressants, alpha-2 adrenergic agonists, cannabinoids, and topical therapies.
Glucocorticoids alleviate symptoms of pain, nausea, fatigue, anorexia, and malaise. In addition, they may be beneficial in neuropathic pain, bone pain, pain secondary to bowel obstruction, duct obstruction, pain caused by lymphedema, and headache caused by elevated intracranial pressure.
Most likely, glucocorticoids act to reduce tumor-related edema and have anti-inflammatory effects as well as direct effects on nociceptive neural systems. Dexamethasone is a first-line agent due to its long half-life and relatively low mineralocorticoid effects. Prednisone and methylprednisolone are also acceptable. Long term toxicity can include myopathy, immunocompromise, and adrenal insufficiency. Usually these toxicities are mitigated by limited life expectancy.
High-dose regimens have been shown to be more effective in relieving pain than lower dose regimens in spinal cord compression However, limited evidence and the potential for dose-related toxicity should be considered when prescribing these drugs.
Antidepressants have been widely studied in patients with chronic pain although relatively few studies have included cancer patients. They are especially effective in the setting of neuropathic pain. The mechanism of action is thought to be enhanced availability of monoamines, decreased norephinephrine reuptake, as well as increased serotonergic and dopaminergic effects in the synapses of the descending pain modulating system.
Analgesic efficacy is best established with tricyclic compounds, serotonin-norepinephrine reuptake inhibitors SNRIs. First line analgesic antidepressants in patients with cancer would be a tricyclic e. Evidence also exists for efficacy of serotonin-selective reuptake inhibitors SSRIs , although these would not be first-line and bupropion 75 mg twice daily , a dopamine reuptake inhibitor.
Dosages may be titrated upwards while monitoring for intolerable side effects 74 , In terms of side effects, tricyclic compounds are relatively contraindicated in patients with severe heart disease, prostatic hypertrophy, and narrow-angle glaucoma. Side effects of SNRIs include nausea, sexual dysfunction, somnolence, and mental clouding.
With up-titration of desipramine, the patient should be monitored for prolongation of QTc interval and the development of cardiac arrhythmias.
While duloxetine and buproprion do not prolong the QTc interval, duloxetine has gastrointestinal side effects including nausea, dry mouth, and constipation and buproprion causes jitteriness and headache. Alpha-2 adrenergic agonists include clonidine and tizanidine. These agents can provide relief in diverse types of pain.
Spinally administered clonidine has been shown to be particularly effective in neuropathic pain relief The mechanism of action of these drugs may be related to increased activity of monoamine-dependent, endogenous pain modulating pathways. Side effects of alpha-2 adrenergic agonists include somnolence, dry mouth, and hypotension. Cannabinoids are derived from the cannabis plant and the primary psychoactive agent is deltatetrahydrocannabinol THC or dronabinol which serves to activate receptors in both the peripheral and central nervous system.
Some evidence shows efficacy in cancer patients 77 although concern regarding their abuse potential has slowed their development. In Canada, nabiximols or sativex is an oromucosal spray containing THS plus other cannabinoids for treatment of neuropathic pain from multiple sclerosis and is also used in cancer patients. In this double-blind trial, cancer patients suffering from ineffective analgesic control of pain symptoms, nabiximols was up titrated and the adjusted mean pain score was significantly reduced in the group taking nabiximols compared to the placebo group though some bias could have been present in terms of differences in baseline opioid dosing in the two groups Nabilone is another cannabinoid that would be considered for cancer patients whose pain is refractory to opioids and after a trial of other adjuvants.
No controlled studies address the efficacy of inhaled marijuana as an adjunct to chronic pain in cancer patients. The side effects from cannabinoids are most commonly dizziness, somnolence, and dry mouth. Despite legalization in the Netherlands, Canada, and several states, in the US, cannabinoids is still illegal at the federal level.
Benefits of using topical therapies as an adjunct to other analgesic include the ability to directly deliver analgesia to the site that is presumably responsible for persistent pain. Lidocaine patches are transdermal patches that can be used for regional pain of all types.
Patients with postherpetic neuralgia 67 , diabetic neuropathy 78 , and osteoarthritis 79 revealed positive impact on pain. Most frequent adverse effects include skin irritation.
Other local anesthetics include EMLA or eutectic mixture of local anesthetics cream 80 , capable of producing dense local cutaneous anesthesia, capsaicin 80 , a naturally occurring compound of the chili pepper, and other drugs that have been compounded into creams for patients with pain including ketamine and gabapentin. Drugs especially appropriate for relieving neuropathic pain include the analgesic antidepressants and anticonvulsants. Duloxetine was shown to have improved quality of life scores, and decreased numbness and tingling in patients with painful chemotherapy induced peripheral neuropathy in a multi-institutional trial conducted by the Cancer and Leukemia Group B There is some evidence for anticonvulsant analgesics effects with gabapentin and pregabalin 82 - Both these drugs act by binding to alpha-2 delta protein modulator of N-type voltage-gated calcium channels which reduced calcium influx into the neuron and therefore lessens depolarization.
They are both excreted by the kidneys and dose reduction is necessary in patients with renal dysfunction. Somnolence, mental clouding, and dizziness are main side effects although edema and weight gain occur less frequently. The starting dose of gabapentin is usually to mg per day while pregabalin is mg daily in two divided doses. Tapering these drugs is preferable in the setting of discontinuation.
Numerous other anticonvulsants have potential analgesic effects including carbamazepine, valproate, and phenytoin, however data are limited. Oxcarbazepine, a metabolite of carbamazepine has similar anticonvulsant properties and a safer pharmacologic profile and has been shown to be effective in trigeminal neuralgia Other drug classes that have some activity for neuropathic pain include tizanide, dronabinol, and topical agents.
A brief intravenous infusion of lidocaine has been shown to give prompt pain reduction in severe neuropathic pain Ketamine, a NMDA receptor antagonist, has been used at subanesthetic doses for severe refractory pain 87 and earlier evidence suggested enhanced control of cancer pain when given with morphine 76 , 88 , 89 , however later trials failed to demonstrate added analgesia 89 - 91 and a Cochrane review 92 concluded that the evidence was insufficient to assess the effectiveness of ketamine.
Regardless of lack of high quality evidence, experts still treat refractory neuropathic pain with ketamine using mainly anecdotal evidence.
Still, delirium and psychotomimetic effects of ketamine are problematic and gradual dose titration may help to reduce some of these adverse effects Patients with bone pain may look to radiation therapy for painful bone metastases as well as kyphoplasty and other spinal surgeries designed to treat pain from malignant spinal fractures.
However, medications can be used to treat pain in patients with metastatic bone disease as well and include glucocorticoids like dexamethasone, osteoclast inhibitors like bisphosphonates, and bone-seeking radionuclides Table 8. Osteoclast inhibitors include bisphosphonates, the use of which is supported by significant data.
These drugs act by directly inhibiting osteoclastic activity, causing apoptosis of osteoclasts, and also stimulating osteoblastic activity. Head to head trials comparing the bisphosphonates are few so choice of bisphosphonate is left to patient and clinical preference and convenience.
Generally, these drugs are well tolerated. Complications may include renal dysfunction, flu-like illness, hypocalcemia, and osteonecrosis of the jaw. Donosumab is a monoclonal antibody targeting receptor activator of nuclear factor kabba B ligand RANKL , a key component in the pathway for osteoclast formation and activation.
Progression of pain was decreased in those receiving donosumab when compared to zoledronic acid in patients with advanced breast cancer and bone metastases In addition, denosumab is not associated with renal dysfunction or with flu-like syndromes, making it a viable alternative for patients who have encountered these adverse effects while using bisphosphonates.
However, the cost of denosumab is substantial compared to bisphosphonates Bone targeting radionuclides include strontium and samarium which selectively deliver radiation to bone metastases. Often used for men with metastatic prostate cancer, this approach is for patients with refractory multifocal bone pain. Many patients with advanced intraabdominal or pelvic tumors have inoperable bowel obstruction and are not appropriate for a stent. In these patients, decompression of gastric contents can be achieved with nasogastric tube or percutaneous gastrostomy tube and management with IV fluids has been conventional approaches.
However, control of pain, distention, and vomiting using medical management may include use of glucocorticoids to decrease edema surrounding the tumor and use of octreotide and anticholinergic agents to lessen intraluminal secretions and peristaltic movements.
Octreotide, dexamthasone, and hyoscine butylbromide are effective at reducing symptoms of bowel obstruction according to one review Scopolamine and glycopyrrolate are also anticholinergic drugs that reduce gut motility and decrease secretions.
Though optimization of opioid therapy and use of adjuvants results in a balance of satisfactory analgesia in many cancer patients, a substantial number unfortunately do not achieve effective pain relief through the medications described above. Interventional pain management strategies include a diverse group of invasive therapies: Evidence for these therapies remain limited, most of which are implemented by those who have received specialized training. Injections into the soft tissue and joints are commonly to address focal musculoskeletal pain and myofascial pain, or pain with distinct trigger points.
Injections can be given epidurally, into facet joints, and into the sacroiliac joints for those with and without cancer related pain. Developed to address pain from vertebral collapse in neoplastic disease to the spine, vertebroplasty is the percutaneous injection of bone cement or methylmethacrylate under fluoroscopic guidance into a collapsed vertebral body while kyphoplasty involves the introduction of inflatable bone tamps, termed balloon kyphoplasty, that restore the height of the vertebral body.
Cancer patients have greater quality of life and sustained improvement in activity over 12 months. However, they also had non-Q wave infarction attributed to anesthesia and cement leakage to the disc as adverse events Direct head-to-head trials with vertebroplasty compared to kyphoplasty are limited. For patients with multiple myeloma and bone disease, pain may be refractory to bisphosphonates, calcitonin, and other opiates.
Guidelines suggest balloon kyphoplasty rather than vertebroplasty for those patients with symptomatic vertebral compression fractures from lytic metastases The term nerve block refers to delivery of an agent or device that modulates nociceptive afferent input to the central nervous system with either a nondestructive analgesic or a neurolytic drug.
A diagnostic nerve block is performed to determine the afferent terminal of the noxious stimulus and can be performed using local anesthetic blocks which affect both sensory as well as motor neural activity.
A diagnostic nerve block can be helpful to clarify if the pain is maintained using sympathetic neurons or transmitted via nociceptors travelling with sympathetic nerves.
A prognostic nerve block is a neurolytic or neurodestructive block that extends relief of pain through the destruction of the nerve and sensory loss. Usually, a local anesthetic nerve block is performed before the neurolytic block to determine if the sensory loss is satisfactory. A block performed using bolus or continuous infusion of local anesthetic is termed non-neurolytic blocks and address pain that is either acute or chronic.
Transitory interruption of the afferent nociceptive input may result in pain relief that outlasts the duration of effect of the anesthetic. In fact, repeated local anesthetic blocks can be a therapeutic strategy towards relieving pain. Delivery of non-neurolytic blocks may be via catheter into the epidural space, to a peripheral nerve, or nerve plexus.
Patients with focal regional pain syndrome may achieve good pain relief with infusion of local anesthetic especially if they have demonstrated prior benefit from bolus injections. Epidural catheters with continuous anesthetic infusions can be performed for those with larger areas of pain and may be combined with opioids.
Case reports have demonstrated anecdotal evidence that such blocks are effective in cancer pain , When pain involves somatic structures, the choice of a sympathetic rather than somatic nerve block may be done if the perception of the pain is thought to be maintained by sympathetic efferent activity.
For example, complex regional pain syndrome is likely characterized by sympathetically-maintained pain. Clues to characterize sympathetically-maintained pain include patients with focal autonomic dysfunction such as vasomotor instability, sweating, increased hair growth, and thinning of the skin. In this case, a trial of sympathetic block may be considered.
Many cancer patients often have difficult to control visceral pain. Sympathetic nerve block is especially appropriate for visceral cancer pain which is often at least somewhat manageable with sympathetic blockade. Blockade of the sympathetic nerve interrupts both the efferent sympathetic and afferent fibers traveling in the same nerve.
Sympathetic blocks are targeted to the anatomic location of the sympathetic nervous system and result in anesthesia of their respective sympathetic nerves Table 9.
These nerve blocks can be done for cancer patients and those without cancer. Both bolus and continuous epidural anesthetic infusions may be used to denervate specific areas of the body. For example, a nerve block at the brachial plexus can denervate the shoulder or arm, a Gasserian ganglion block can be used to denervate part of the face. Neurolytic techniques destroy afferent neural pathways including somatic and sympathetic efferents and employ surgery, cryotherapy, radiofrequency thermal coagulation, or chemical neurolysis using alcohol or phenol.
Traditional methods for neurolytic nerve block include phenol and alcohol. Newer approaches include nondestructive analgesics. Given neurolysis results in destruction of the nerve, regeneration may occur if axolemma are intact after months and can lead to functional recovery of the nerve.
After neurolysis, deafferentation pain syndrome may manifest as an adverse effect and may be as difficult to treat as the initial pain syndrome. For this reason, neurolysis is considered a last resort therapy. Therapeutic strategies for neurolysis include the celiac plexus for pain originating from upper abdominal malignancy, especially pancreatic cancer.
Superior hypogastric plexus neurolysis may be considered for visceral pelvic pain refractory to opioid interventions. Implanted catheters may be used to deliver infusions of local anesthetic for analgesic purposes. These strategies avoid side effects associated with systemic medications but adverse effects include infection and the possibility of mechanical failure.
Dorsal column stimulation is the most common type of implanted neurostimulatory treatment. An electrode is passed into the epidural space at the level of desired analgesia. When an electrical current is applied, paresthesias and sometimes analgesia localized to the region of pain provide relief. Overall, analgesic use is reduced when using spinal cord stimulation when treating refractory cancer-related pain Those patients with debilitating cancer pain of neuropathic origin and who are at the end of life are likely the most appropriate candidates for spinal cord stimulation.
Infusion of drugs into the epidural or intrathecal space is termed neuraxial infusion. If the patient is likely to survive for months, a catheter can be tunneled under the skin and can deliver medications via an external pump or a fully implanted infusion pump.
Epidural drug delivery necessitates higher drug doses but permits delivery to fewer dermatomes while intrathecal infusion delivers far less drug to achieve a comparable level of anesthesia.
The frequency of pain relief, however, is similar with both strategies Morphine, targeting receptors in the dorsal horn, and bupivicaine, which inhibits sodium channels in spinal nerve roots, have been used commonly in neuraxial infusions and work synergistically to relieve neuropathic pain Epidural clonidine can be added to morphine infusions and can be effective in some patients with neuropathic cancer-related pain and intrathecal baclofen is sometimes used as well. In addition, ziconotide, a neural N-type calcium channel blocker, can be used in those patients who are refractory to intrathecal morphine treatment for cancer pain.
Patients had less fatigue, depressed level of consciousness, and a trend toward higher survival rates at 6 months. In addition there was a trend towards improved survival at six months Risks of indwelling catheter lines include infections like epidural abscess and meningitis, bleeding, respiratory depression especially in those patients who are opioid-naive, blockade of both sensory nerves causing unpleasant numbness and proprioceptive, motor blockade causing weakness, sympathetic blockade causing hypotension.
Complications can be minimized with low initial drug dosing and careful uptitration with close monitoring for potentially life-threatening effects. Hygroma and pump pocket seromas may occur after pump placement but in most cases, self-resolve. Intraventricular opioid delivery with morphine can be used for patients using an Omaya reservoir and can result in good initial pain relief. However, the evidence for this is limited and there are associated adverse effects including respiratory depression, sedation, and confusion as compared to the epidural or intrathecal route There remain a small percentage of patients who experience severe unrelenting pain at the end of life, despite appropriate pharmacologic and non-pharmacologic approaches.
When this is the case sedation may be considered. At the end of life, when the overwhelming goal of care is preservation of patient comfort, the provision of adequate relief of symptoms must be pursued even in the setting of a narrow therapeutic index for the necessary palliative treatments.
Opioids, adjuvants, and interventional options for pain management of symptomatic metastases
Professional and collegial interactions with all members of our care teams Bottom line, I don't expect to be writing prescriptions for CBD-based medications . Doctors cannot prescribe marijuana under a Supreme Court decision. Baltimore as well as other hospitals and medical facilities, and MedStar Health who normally rely on extensive study on dosing, interactions with. [email protected] .. Establishing a therapeutic relationship is built upon with each interaction. .. However, limited evidence and the potential for dose- related toxicity should be considered when prescribing these drugs. .. study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with.