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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
March 24, 2018

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Are Opioids Beneficial for Chronic Back and Osteoarthritis Pain?
Understanding Barriers to Primary Medication Adherence for Children
Stimulant Use for ADHD Not Associated with Elevated Seizure Risk
Does Endoscopic Surveillance of Barrett Esophagus Save Lives?
Is There an Optimal Treatment for High-Risk Prostate Cancer?
Breast Cancer Outcomes in BRCA-Mutation Carriers
Alternative Exam Uptake in Patients with Positive FOBT Who Refuse Colonoscopy
Women's Sexuality in Midlife: It's Not All Downbeat
Stroke Risk Factors, Treatments, and Outcomes for Women
How to try Edible Cannabis Without Feeling Like You're Going to Die

JAMA 2018 Mar 6; 319:872
Are Opioids Beneficial for Chronic Back and Osteoarthritis Pain?
This Veterans Affairs study showed no benefit over nonopioid medication regimens.
Although most clinical guidelines recommend against opioids for patients with chronic back and musculoskeletal pain, opioids still are prescribed frequently for these conditions. In this randomized trial, conducted in the Minneapolis Veterans Affairs system, researchers randomized 240 patients (mean age, 58; mostly men) with moderate-to-severe chronic back pain or hip or knee osteoarthritis pain to flexible opioid or nonopioid regimens. Patients who were receiving long-term opioid therapy were excluded, as were those with substance abuse disorders or poor prognoses.
Opioid regimens started with immediate-release morphine or oxycodone or hydrocodone/acetaminophen and progressed to sustained-action morphine or oxycodone or transdermal fentanyl, all titrated to 100-mg morphine-equivalents, as needed. Nonopioid regimens started with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and progressed to tricyclic antidepressants, gabapentinoids, topical analgesics, serotonin-norepinephrine reuptake inhibitors, and tramadol as needed. Patients pursued nonpharmacologic treatments as desired. Both groups were monitored in-person monthly until stable; subsequently, patients were monitored every 1 to 3 months (usually by telephone).
At 12 months, improvement in pain-related function was similar between the two groups. Pain intensity was significantly lower in the nonopioid group than in the opioid group, although this improvement was of borderline clinical significance. The opioid group had significantly more medication-related symptoms; adverse events did not differ between groups.
COMMENT: This nonblinded trial mimics real-life practice with its patient heterogeneity and wide range of medication choices. No benefit, and some potential harm, seems to be associated with use of opioids in patients with chronic back or osteoarthritis pain. Note, however, that several of the medications used by patients in this study's control group — including acetaminophen, NSAIDs, and gabapentinoids — also are ineffective or minimally effective in patients with chronic low back pain.
(NEJM JW Gen Med Jan 1 2018).
CITATION(S): Krebs EE et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA 2018 Mar 6; 319:872. (http://dx.doi.org/10.1001/jama.2018.0899)
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Pediatrics 2018 Mar 16
Understanding Barriers to Primary Medication Adherence for Children
Pharmacies in zip codes with high poverty or low vehicle ownership had the highest rates of unfilled prescriptions.
Primary medication nonadherence (failure to fill a newly prescribed medication) occurs in up to 25% of high-risk patients and is a cause of preventable morbidity. Poverty-related stressors have been linked to nonadherence in prior studies, although none utilized pharmacy records to examine its local determinants. In the current study, researchers used electronic prescription data from one large pharmacy chain in a single metropolitan area along with census data to assess whether a patient's neighborhood characteristics or the type of medication prescribed is associated with nonadherence.
The researchers analyzed nearly 214,000 new prescriptions for patients aged 0 to18 years over a 6-month period. Primary nonadherence (defined here as not picking up a prescription within 30 days) occurred in 12% of prescriptions. Nonadherence rates varied across zip codes, from 7% to 26%; unfilled prescriptions were 60% more likely in zip codes with the highest versus lowest poverty rates, and 77% more likely in zip codes with lowest versus highest vehicle ownership. Nonadherence rates were higher in for boys than girls, older versus younger children, and those with public versus private insurance. By prescription type, nonadherence rates were lowest for oral anti-infectives (4%) and highest for nutritional medications (29%).
COMMENT: Medication nonadherence might worsen existing health disparities and therefore could be addressed through systematic changes to how prescriptions are dispensed — particularly for high-prevalence conditions such as asthma or attention-deficit/hyperactivity disorder. For example, some pharmacies linked with community health centers provide home delivery of prescriptions. When transportation has been a barrier to attending appointments, pediatricians should consider asking parents whether barriers exist to picking up prescriptions as well.
CITATION(S): Hensley C et al. Poverty, transportation access, and medication nonadherence. Pediatrics 2018 Mar 16; [e-pub].
(http://dx.doi.org/10.1542/peds.2017-3402)
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Neurology 2018 Feb 23
Stimulant Use for ADHD Not Associated with Elevated Seizure Risk
Reassuring evidence on the safety of medications for attention-deficit/hyperactivity disorder should be shared with patients.
There is concern that stimulant medication may increase the risk for seizures, despite some evidence demonstrating its safety (e.g., methylphenidate in patients with uncontrolled epilepsy; NEJM JW Psychiatry Aug 2011 and Epilepsy Behav 2011; 21:228). In the current study, researchers examined the risk for seizures among over 800,000 individuals (aged 5–64 years) who received a new diagnosis of attention-deficit/hyperactivity disorder (ADHD) or a prescription for an ADHD medication, based on health insurance claims data. Selected patients also had no claims for seizures for at least 1 year before diagnosis or prescription receipt.
Seizures occurred in approximately 2% of the ADHD cohort (men, 1.8%; women, 2.1%) compared with less than 1% of a matched control group (odds ratio, 2.3 for men and women). Those who were never prescribed ADHD medications had a higher risk for seizure compared with those ever prescribed an ADHD drug. Comparing nonmedicated and medicated months among all ADHD patients, the odds of seizure were approximately 40% lower during medicated months. In comparisons of nonmedicated and medicated months for individual patients, odds of seizures were lower while on medicine — by 29% among those with a seizure history and by 49% in those with no seizure history. The prescription of ADHD medications for 2 cumulative years was not associated with seizure risk.
COMMENT: This large database study, like other recent reports, demonstrates no increased risk for seizures with the use of ADHD medications. While ADHD itself is associated with seizures, ADHD medications may decrease the occurrence of seizures. The FDA labeling of these medications concerning the risk for seizures needs revision. This is an important study to discuss with our patients.
CITATION(S): Wiggs KK et al. Attention-deficit/hyperactivity disorder medication and seizures. Neurology 2018 Feb 23; [e-pub].
(https://doi.org/10.1212/WNL.0000000000005213)
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Gastroenterology 2018 Feb 17
Does Endoscopic Surveillance of Barrett Esophagus Save Lives?
Mortality benefits shown in meta-analyses of observational study data were mostly explained by lead-time and length-time biases.
Controversy continues as to whether surveillance for dysplasia and esophageal adenocarcinoma (EAC) in patients with Barrett esophagus (BE) is cost-effective or preventative. In the current comprehensive systematic review and meta-analyses, surveillance of patients with BE was associated with lower EAC-related mortality (relative risks from different meta-analyses, 0.60 and 0.73) and all-cause mortality (hazard ratios, 0.75 and 0.48) and greater likelihood of EAC diagnosis at early stages of 0 and 1 (RRs, 2.1 and 5.5). However, adjustments for lead-time and length-time biases reduced or eliminated observed benefits in most analyses.
COMMENT: To date, we lack randomized, controlled trial data to best evaluate the efficacy of routine endoscopic surveillance (as mentioned in this review, one randomized, controlled trial is currently underway in the U.K.). As national guidelines presently recommend surveillance for all patients with BE, clearly better risk stratification is needed.
Until we have better direction, clinicians should understand that the standard of care is for high-quality examination using white-light endoscopy (ideally high-definition) with appropriate biopsy sampling and awareness of adjunctive measures (e.g., narrow-band imaging) to direct targeted additional biopsies. Removal of mucosal debris, insufflation and deflation of the esophagus, and retroflexed evaluation of the esophagogastric junction should be a priority for quality care, as well as longer time of exam, which has correlated with better high-grade dysplasia detection. For patients with newly diagnosed BE without dysplasia (as determined with appropriate biopsy sampling), routine endoscopy at 1 year is no longer recommended, and surveillance at 3-to-5-year intervals should be standard but determined within the context of comorbidities and life expectancy (similar to the process for colon cancer screening). Although there are identified risk factors suggested for progression of dysplasia and neoplasia (NEJM JW Gastroenterol Mar 2018 and Clin Gastroenterol Hepatol 2017 Nov 30; [e-pub]), we are not yet at the stage to discontinue surveillance except in selected patients.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Codipilly DC et al. The effect of endoscopic surveillance in patients with Barrett's esophagus: A systematic review and meta-analysis. Gastroenterology 2018 Feb 17; [e-pub].
(https://doi.org/10.1053/j.gastro.2018.02.022)
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JAMA d 2018 Mar 6; 319:896
Is There an Optimal Treatment for High-Risk Prostate Cancer?
External beam radiotherapy plus brachytherapy boost and androgen deprivation therapy outperformed other modalities in a retrospective study.
The management of patients with high-risk localized prostate cancer typically requires multimodality therapy. However, the optimal approach remains undefined.
To address this issue, investigators conducted an international, retrospective cohort study involving 1809 men treated for high-risk prostate cancer (Gleason score, 9–10) between 2000 and 2013. Of these patients, 639 underwent radical prostatectomy (RP), 734 underwent external beam radiotherapy (EBRT), and 436 underwent EBRT plus brachytherapy boost (EBRT+BT). Most EBRT and EBRT+BT patients received androgen deprivation therapy (ADT; 89.5% and 92.4%, respectively), but EBRT+BT patients had a shorter median duration of ADT than did EBRT patients (12.0 vs. 21.9 months; P<0.001).
The 5-year incidence rates of prostate cancer–specific mortality (the primary outcome) for RP, EBRT, and EBRT+BT were 10%, 11%, and 3%, respectively; EBRT+BT was associated with a significantly reduced risk for prostate cancer–specific mortality compared with RP or EBRT (P<0.001). Adjusted 5-year incidence rates of distant metastases for RP, EBRT, and EBRT+BT were 24%, 24%, and 8%, respectively. No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality were found between EBRT and RP.
COMMENT: Given the retrospective design of this study, the authors acknowledge that it cannot adequately capture comorbidity issues that complicate comparisons between EBRT and EBRT+BT. In addition, toxicity and patient-reported outcomes were not available. Despite these limitations, the results are provocative and may inform practice, as prospective testing in this narrow disease subset will never be conducted.
CITATION(S): Kishan AU et al. Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9–10 prostate cancer. JAMA 2018 Mar 6; 319:896.
(https://doi.org/10.1001/jama.2018.0587)
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Endoscopy 2018 Feb 27
Breast Cancer Outcomes in BRCA-Mutation Carriers
Overall survival at 2, 5, and 10 years was similar between carriers and noncarriers.
Previous reports describing the outcomes of young women diagnosed with early-stage breast cancer and BRCA germ-line mutations have not been consistent. Some have suggested a worse prognosis for these patients than for those with sporadic disease, whereas other studies have reported no differences in outcomes between the two types of patients. These discordant results may be explained in part by methodological differences, sample size variability, and variance in genotyping.
To examine this disparity further, investigators conducted a multicenter, prospective cohort study (POSH) involving 2733 patients (age, ≤40 years) who were recruited within 1 year of receiving a diagnosis of early-stage breast cancer. Genotyping identified a pathogenic BRCA mutation in 338 patients (12%). Among 558 patients (20%) with triple-negative breast cancer (TNBC), 136 (24%) had a BRCA mutation. In addition to receiving local therapy, the vast majority of patients received adjuvant chemotherapy. Risk-reducing bilateral mastectomies were performed infrequently.
At a median follow-up of 8.2 years, overall survival (OS; the primary endpoint) was similar between mutation carriers and noncarriers at 2 years (97.0% and 96.6%, respectively), as well as at 5 years (83.8% and 85.0%) and 10 years (73.4% and 70.1%). Among 558 TNBC patients, mutation carriers had a better OS compared with noncarriers at 2 years (95% vs. 91%; P=0.047), but not at 5 or 10 years.
COMMENT: Based on its size, contemporary BRCA testing, and follow-up period, the POSH study provides clearer insight into the expected prognosis of BRCA-mutation carriers with early-stage breast cancer. The finding of essentially equal outcomes with standard therapy across the overall population is reassuring, and now that newer agents such as PARP inhibitors are being evaluated, there is a prospect of even better results. The observation of improved OS early on for the mutation-positive TNBC subset is intriguing and suggests many possible explanations that will be verified or disproven only with additional study. Finally, whether ablative, risk-reducing surgery is absolutely necessary early after diagnosis is also challenged by these results.
CITATION(S): Copson ER et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): A prospective cohort study. Lancet Oncol 2018 Feb; 19:169.
(https://doi.org/10.1016/S1470-2045(17)30891-4)
Fasching PA. Breast cancer in young women: Do BRCA1 or BRCA2 mutations matter? Lancet Oncol 2018 Feb; 19:150.
(https://doi.org/10.1016/S1470-2045(18)30008-1)
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Endoscopy 2018 Feb 27
Alternative Exam Uptake in Patients with Positive FOBT Who Refuse Colonoscopy
Very few patients completed video capsule endoscopy or computed tomographic colonography upon invitation in a randomized trial.
Patients with a positive fecal occult blood test (FOBT) should undergo colonoscopy, and those who refuse are at high risk for developing symptomatic colorectal cancer, which may be advanced at presentation. Rates of colonoscopy refusal in programmatic FOBT screening range from 10% to over 30%.
In a study conducted in France, over 750 patients with positive FOBT who refused colonoscopy were randomized to receive an invitation letter for video capsule endoscopy (VCE) or computed tomography colonography (CTC). The procedure completion rate was similar between groups (5% for VCE and 7% for CTC). An additional 30 patients underwent colonoscopy after the invitation, without undergoing either VCE or CTC. Potentially neoplastic lesions were discovered in 12 of 19 VCE patients (60%) and 8 of 28 CTC patients (29%).
COMMENT: In recent studies comparing VCE and CTC, VCE has tended to identify more clinically significant polyps than CTC. However, neither exam was an effective means of completing imaging in patients with a positive FOBT who refused colonoscopy, as both had low adherence rates. These patients continue to represent a significant management challenge.
CITATION(S): Pioche M et al. Colon capsule versus computed tomography colonography for colorectal cancer screening in patients with positive fecal occult blood test who refuse colonoscopy: A randomized trial. Endoscopy 2018 Feb 27; [e-pub].
(https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0044-100721)
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Menopause 2018 Mar; 25:286
Women's Sexuality in Midlife: It's Not All Downbeat
Qualitative study revealed both positive and negative changes and adaptations to achieve a satisfying sex life.
Longitudinal studies of women's sexuality in midlife, particularly around menopause, have relied on standardized questions and generally indicate negative changes (decrease in libido, arousal, and lubrication; increase in painful intercourse). Now, researchers applied a qualitative open-ended approach to reveal nuances of sexuality changes in midlife. A total of 39 women (mean age, 52; 54% white; sexual activity with a partner at least once during the preceding 12 months) participated in one-on-one interviews or focus groups with trained interviewers.
Reported negative changes included decreased sexual frequency (which some considered positive), libido, and vaginal lubrication as well as orgasm difficulties attributed to physical (fatigue, menopause, pain), psychosocial (career, financial and family stress, body image), or partner (health, sexual dysfunction) changes. Positive changes or improvements in sexual function were attributed to stronger emotional connection due to increased self-knowledge, communication, and self-confidence. Women adapted to both negative and positive changes by changing their sexual behavior and prioritizing different aspects of sex (e.g., nonpenetrative sex, emotional closeness, position changes).
COMMENT: This study is limited by the small number of participants willing to candidly discuss sexual issues. However, the findings offer insights for women and clinicians — particularly the recognition that not all midlife sexuality changes are negative, and not all negative changes require medical intervention. The challenge is for us to address sexuality issues, both offering medical interventions and suggesting that communicating sexual needs and making adaptations can be successful strategies for a fulfilling sex life through midlife and beyond.
CITATION(S): Thomas HN et al. Changes in sexual function among midlife women: “I'm older… and I'm wiser”. Menopause 2018 Mar; 25:286.
(https://doi.org/10.1097/GME.0000000000000988)
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Stroke 2018 Mar; 49:524
Stroke Risk Factors, Treatments, and Outcomes for Women
A set of focused updates highlights current knowledge and reveals gaps in our understanding of how stroke affects men and women differently.
Women bear a disproportionate burden of disease from stroke. Certain stroke risk factors, treatments, and outcomes affect women and men differently. Among the potential explanations for these disparities are the differential effects of conventional stroke risk factors; the influence of sex-specific risk factors such as pregnancy, preeclampsia, and fluctuations in hormone levels; variances in the efficacy or application of interventions for stroke prevention and treatment; and differences in how stroke affects long-term function and disability outcomes. There are gaps in our understanding of these factors as well as of how women are affected by stroke and how a more tailored approach to stroke risk assessment, prevention, and treatment for women may be beneficial.
One reason for these knowledge gaps is that, although pivotal sex-specific trials and large cohort studies have provided key insights into these issues, women continue to be underrepresented in cardiovascular and stroke trials. Moreover, even in studies not specifically designed to evaluate sex disparities, opportunities to report sex-specific associations are often missed.
In the February issue of Stroke, coinciding with the Go Red for Women campaign by the American Heart Association and the American Stroke Association, four articles and an accompanying editorial provide a focused update on the medical literature regarding stroke in women.

A common theme across these updates is that while we have gained certain insights about stroke in women, important questions remain.
For example, we have ample evidence that hypertensive disorders of pregnancy, including preeclampsia, confer a substantially increased relative risk for ischemic and hemorrhagic stroke.1 The current mainstays for peripartum management of these disorders include:

However, these recommendations are based on only hints about the underlying pathophysiology of preeclampsia that are suggested by parallels with PRES and RCVS; a precise understanding of the basic mechanisms that result in preeclampsia remains elusive. Moreover, our understanding about prognosis is incomplete, since we do not have a clear answer about whether the risk for future ischemic stroke is independently increased by a previous history of preeclampsia.
With regard to other sex-specific risk factors, we know that endogenous estrogen levels are not associated with stroke risk, but exogenous estrogen supplementation with oral contraceptives, particularly for current smokers, and hormone replacement therapy are associated with increased stroke risk.2 In fact, these findings are often cited as an example of the sobering discrepancy between what was suggested by multiple high-quality observational studies (lower stroke risk with estrogen) and what was ultimately demonstrated by randomized clinical trials (higher stroke risk with estrogen). But precise evaluation of the strategy of using progestin-only contraceptives for women with coexisting stroke risk factors requires further research.
Regarding traditional stroke risk factors in women, we know that hypertension is less common and blood pressure control is more common in women than men up to the sixth decade of life, but there is a higher prevalence of hypertension and poorer blood pressure control thereafter.3 And although we suspect that the slower decline in stroke rates in women versus men may be explained in part by rising rates of diabetes — facilitated by the stronger association between diabetes mellitus and stroke risk among women than men — we do not have a full understanding why statins, oral anticoagulants for atrial fibrillation, or cardiac ablation procedures are not used as often for women as for men.
After a stroke has occurred, women appear to have more activity limitations than men, largely driven by worse outcomes, as measured by the modified Rankin Scale or Barthel Index.4 Also, poststroke depression and health-related quality of life are worse in women. But because the magnitude of these differences is attenuated after accounting for other factors, much work needs to be done to disentangle the influence of sex from other factors, including older age at stroke, worse prestroke function, and musculoskeletal issues such as osteoporosis and arthritis among women with stroke.
COMMENT: Clinicians should consider stroke risks when prescribing oral contraceptives, review current recommendations for stroke prevention during pregnancy, and, when treating transgender patients, understand the stroke risks in those taking estrogen. Clinicians should also be mindful of opportunities to intensify screening for and treatment of stroke risk factors in women and to anticipate the often greater impact of stroke on outcomes in women.
A specific focus on understanding stroke in women through clinical trials and cohort studies is crucial, as is expanding interest in women and stroke among the community of investigators and of decision makers who are setting research agendas. A concerted effort to increase enrollment of women in clinical trials, initiate studies specifically designed to evaluate sex differences in stroke, find opportunities to report sex-specific associations and tests of interaction by sex, and focus on the pipeline of women in research will be important given the scope of the task at hand.
CITATION(S):
1. McDermott M et al. Preeclampsia: Association with posterior reversible encephalopathy syndrome and stroke. Stroke 2018 Mar; 49:524.
(http://dx.doi.org/10.1161/STROKEAHA.117.018416)
2. Demel SL et al. Stroke risk factors unique to women. Stroke 2018 Mar; 49:518.
(http://dx.doi.org/10.1161/STROKEAHA.117.018415)
3. Madsen TE et al. Impact of conventional stroke risk factors on stroke in women: An update. Stroke 2018 Mar; 49:536.
(http://dx.doi.org/10.1161/STROKEAHA.117.018418)
4. Gall S et al. Focused update of sex differences in patient reported outcome measures after stroke. Stroke 2018 Mar; 49:535.
(http://dx.doi.org/10.1161/STROKEAHA.117.018417)
Kaplovitch E and Anand S. Stroke in women: Recognizing opportunities for prevention and treatment. Stroke 2018 Mar; 49:515.
(http://dx.doi.org/10.1161/STROKEAHA.117.020354)
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How to try Edible Cannabis without Feeling Like You're Going to Die
By ROBIN ABCARIAN
MAR 19, 2018  robin.abcarian@latimes.com
One evening late last year I was on my computer at home when I heard a woman yelling. Well, not just yelling. More like screaming bloody murder.
I ran outside and discovered the noise was coming from the house next door. I bounded in and found my neighbor in her bedroom, alternately curled on her bed, then sitting up screaming. Her dogs were cowering.
She had bitten off a chunk of a cannabis-infused caramel that contained a total of 100 milligrams of THC. She had probably consumed between 10 milligrams and 15 milligrams. A standard dose for experienced users is around 10 milligrams, but as a cannabis expert friend of mine says, "Your mileage may vary."
Having spent the last couple of years learning about cannabis, I knew that she was not going to die. But she was in such distress that I suggested that her husband call 911.
"As a business owner, those are the nightmare scenarios that we have worked really hard to prevent over the years," said Kristi Knoblich, who, along with her husband, Scott Palmer, own Kiva Confections, one of the largest edible cannabis companies in the state. "You may feel like you are going to die, but you are not going to die — that's not great marketing language."
As California enters the brave and complex world of cannabis legalization, it's important that consumers who choose to experiment with pot understand how to avoid ending up like my neighbor. Inexperienced users who want to dabble, especially with edibles, owe it to themselves to get educated.
"Dosing and storage are the two areas we need to bring awareness to," Knoblich said.
The state's Bureau of Cannabis Control and the Department of Public Health have created rules and regulations designed to keep the public safe. But the public, obviously, has an obligation to keep itself safe too.
The rules cover all aspects of the manufacturing process, including product design (edibles cannot be packaged in a way that is attractive to children, nor can the product itself look like kids' candy). And there are stringent requirements for child-resistant packaging, which are adding considerably to the cost of every product.
"'Child resistance' is a really nice talking point," Knoblich said. "It sounds great on paper. But, honestly, parents need to lock this stuff up. Like their guns and their alcohol cabinet. Cannabis needs to be in an area that is completely inaccessible to children."
The new law says that one serving of an edible can contain no more than 10 milligrams of THC, the psychoactive ingredient in cannabis, with no more than 100 mgs allowed in a single product package.
(Think of a segmented chocolate bar.)
But for inexperienced users, 10 milligrams is probably way too much.
Knoblich and her husband are proponents of microdosing. Generally, a microdose is defined as an amount between 2.5 milligrams and 5 milligrams of THC.
"It's difficult to explain to people what the effects are going to be, but I try to use a glass of wine analogy," Knoblich said as we sat in the conference room of her factory in West Oakland last month.
"A microdose of 2.5 milligrams may be like one glass of wine for someone, and 5 milligrams might be like two glasses of wine. The frustrating part about cannabis is that every amount affects everybody differently, so you run the risk of not feeling it, then getting frustrated. And then you want to take more, which can be a mistake."
Indeed.
Although a glass of wine goes to your head immediately, it can take up to two hours to feel the full effect of an edible. This is where so many people get into trouble.
"There is not a lot of research on how external factors affect you, but food in your stomach, what your metabolism is like, and alcohol, can add to the intensity of the effects," Knoblich said. "Two hours is a realistic amount of time to wait to see."
Also, if I may: Don't ever eat homemade marijuana brownies. You have no idea how much THC you are getting, and you may end up feeling as if you are going to die.
::
One major byproduct of legalization has been the dramatic increase in the cost of doing business. All marijuana entrepreneurs must obtain local and state licenses, which are expensive.
Taxes have been levied on cannabis at nearly every point between cultivation and retail sales. In addition to state taxes, cities and counties can impose taxes of their own. Oakland, for example, where Kiva is based, levies a 10% tax on gross receipts, which has prompted the company to look for a location in a lower-tax city. To keep and attract cannabis businesses, the city of Berkeley recently slashed its tax from 10% to 5%.
For consumers, all the taxes mean retail prices have spiked, even as the wholesale price of raw cannabis has plummeted.
One of Kiva's most popular products, a small round tin containing chocolate-covered blueberries (each berry has 5 milligrams of THC and can easily be cut in half) retailed last year for about $19. This year, the same tin retails for closer to $30.
"The most poignant piece of feedback we got from a consumer is, 'If I had known that prices are going to be this high in the regulated market, I wouldn't have voted to legalize cannabis,'" Knoblich said.
::
Shortly after we called 911, the paramedics arrived.
By their demeanor, I could see there was nothing special about this "emergency."
My neighbor's vitals were fine, and she had calmed down. She declined an offer to be transported to the ER. But one of the paramedics said something that upset her, and she started screaming again, so they took her anyway. After a few hours of observation, she was sent home.
The next morning she was a little embarrassed but fine. She told me that she had hallucinated that her contractor was trying to steal her home out from under her.
As I told the story to Knoblich, I found myself chuckling.
"I don't want to downplay the severity of feeling like you are out of control," Knoblich said. "But a lot of people present these stories the way you did: 'This happened to my neighbor, it was absolutely terrible,' and when you get to the end of the story, you're kind of laughing.
 
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